![]() ; ; et al in Biochemical and biophysical research communications (2016), 470(3), 678-84 The endogenous cannabinoid 2-arachidonoyl glycerol (2-AG) is an anti-fibrotic lipid mediator that induces apoptosis in hepatic stellate cells (HSCs), but not in hepatocytes. However, the exact molecular ... [more ▼] The endogenous cannabinoid 2-arachidonoyl glycerol (2-AG) is an anti-fibrotic lipid mediator that induces apoptosis in hepatic stellate cells (HSCs), but not in hepatocytes. However, the exact molecular mechanisms of this selective induction of HSC death are still unresolved. Interestingly, the inducible isoform of cyclooxygenase, COX-2, can metabolize 2-AG to pro-apoptotic prostaglandin glycerol esters (PG-GEs). We analyzed the roles of COX-2 and endocannabinoid-derived PG-GEs in the differential susceptibility of primary activated HSCs and hepatocytes toward 2-AG-induced cell death. HSCs displayed significant COX-2 expression in contrast to hepatocytes. Similar to 2-AG, treatment of HSCs with PGD2-GE dose-dependently induced cell death independently from cannabinoid receptors that was accompanied by PARP- and caspase 3-cleavage. In contrast to 2-AG, PGD2-GE failed to induce significant ROS formation in HSCs, and depletion of membrane cholesterol did not rescue HSCs from PGD2-GE-induced apoptosis. These findings indicate differential engagement of initial intracellular signaling pathways by 2-AG and its COX-2-derived metabolite PGD2-GE, but similar final cell death pathways. Other PG-GEs, such as PGE2-or PGF2alpha-GE did not induce apoptosis in HSCs. Primary rat hepatocytes were mainly resistant against 2-AG- and PGD2-GE-induced apoptosis. HSCs, but not hepatocytes were able to metabolize 2-AG to PGD2-GE. As a proof of principle, HSCs from COX-2(-/-) mice lacked PDG2-GE production after 2-AG treatment. Accordingly, COX-2(-/-) HSCs were resistant against 2-AG-induced apoptosis. In conclusion, the divergent expression of COX-2 in HSCs and hepatocytes contributes to the different susceptibility of these cell types towards 2-AG-induced cell death due to the generation of pro-apoptotic PGD2-GE by COX-2 in HSCs. Modulation of COX-2-driven metabolization of 2-AG may provide a novel physiological concept allowing the specific targeting of HSCs in liver fibrosis. [less ▲] Detailed reference viewed: 129 (1 UL)![]() Jeusette, Julien ![]() in Travaux en cours (2016), 12 Between 1923 and 1934, Philippe Soupault published thirteen novels which all have in common the recurring theme of escape. Rather than engaging with the surrealist theme of imaginary escape, the author ... [more ▼] Between 1923 and 1934, Philippe Soupault published thirteen novels which all have in common the recurring theme of escape. Rather than engaging with the surrealist theme of imaginary escape, the author explores real-life leaps into the unknown. A range of characters leave their families, wives, habits and jobs to experience greater freedom and escape the constraints of bourgeois society. Adopting a contextual and sociocritical approach, this paper will focus on Soupault's first novel, Le Bon Apôtre, in order to examine this desire for escape. [less ▲] Detailed reference viewed: 93 (2 UL)![]() ; Nguyen, Duy Cu ![]() ![]() in Proceedings of the 31th IEEE/ACM International Conference on Automated Software Engineering (2016) Security testing is a pivotal activity in engineering secure software. It consists of two phases: generating attack inputs to test the system, and assessing whether test executions expose any ... [more ▼] Security testing is a pivotal activity in engineering secure software. It consists of two phases: generating attack inputs to test the system, and assessing whether test executions expose any vulnerabilities. The latter phase is known as the security oracle problem. In this work, we present SOFIA, a Security Oracle for SQL-Injection Vulnerabilities. SOFIA is programming-language and source-code independent, and can be used with various attack generation tools. Moreover, because it does not rely on known attacks for learning, SOFIA is meant to also detect types of \sqli attacks that might be unknown at learning time. The oracle challenge is recast as a one-class classification problem where we learn to characterise legitimate SQL statements to accurately distinguish them from \sqli attack statements. We have carried out an experimental validation on six applications, among which two are large and widely-used. SOFIA was used to detect real \sqli vulnerabilities with inputs generated by three attack generation tools. The obtained results show that SOFIA is computationally fast and achieves a recall rate of 100\% (i.e., missing no attacks) with a low false positive rate (0.6\%). [less ▲] Detailed reference viewed: 350 (30 UL)![]() ; ; Moes, Michèle ![]() in Oncogene (2016), 35(5), 670 Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs ... [more ▼] Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3'-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome. [less ▲] Detailed reference viewed: 139 (4 UL)![]() Williams, Evan ![]() in Science (2016), 352(6291), 0189 Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across ... [more ▼] Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptomics, and other technologies, transomic data sets can be generated that permit detailed analyses across broad molecular interaction networks. Here, we examine mitochondrial links to liver metabolism through the genome, transcriptome, proteome, and metabolome of 386 individuals in the BXD mouse reference population. Several links were validated between genetic variants toward transcripts, proteins, metabolites, and phenotypes. Among these, sequence variants in Cox7a2l alter its protein's activity, which in turn leads to downstream differences in mitochondrial supercomplex formation. This data set demonstrates that the proteome can now be quantified comprehensively, serving as a key complement to transcriptomics, genomics, and metabolomics--a combination moving us forward in complex trait analysis. [less ▲] Detailed reference viewed: 79 (5 UL)![]() ![]() Andersen, Katja Natalie ![]() in Grucza, Sambor; Olpinska-Szkielko, Magdalena; Romanowski, Piotr (Eds.) Advances in understanding multilingualism: A global perspective (2016) Detailed reference viewed: 120 (13 UL)![]() Andersen, Katja Natalie ![]() Book published by Kohlhammer (2016) Während der Kindergarten eine selbstverständliche Domäne des kindlichen Spiels darstellt, ist die Bedeutung des Spiels in der Grundschule als produktives Element der Didaktik des Unterrichts bis heute ... [more ▼] Während der Kindergarten eine selbstverständliche Domäne des kindlichen Spiels darstellt, ist die Bedeutung des Spiels in der Grundschule als produktives Element der Didaktik des Unterrichts bis heute kaum ins Blickfeld getreten. Das Buch fragt nach der Bedeutung des Spiels in der Schule und nach Spielformen, die sich produktiv im Unterricht einsetzen lassen. Es führt dafür das theoretische Wissen über die Struktur des Spiels mit dem Wissen um die kindliche Erkenntnistätigkeit im Rahmen einer qualitativ-empirischen Studie zusammen und entwickelt Grundsätze der Unterrichtsgestaltung in der Grundschule, um Elemente des Spielens und Erkennens im Unterricht zu verknüpfen. [less ▲] Detailed reference viewed: 228 (10 UL)![]() Gadyatskaya, Olga ![]() ![]() ![]() in Quantitative Evaluation of Systems - 13th International Conference (2016) Detailed reference viewed: 202 (8 UL)![]() ; ; et al in Applied Surface Science (2016), 389 Detailed reference viewed: 168 (2 UL)![]() Merkulov, Sergei ![]() in Letters in Mathematical Physics (2016), 106(2), 169-195 Using the theory of props we prove a formality theorem associated with universal quantizations of Lie bialgebras. Detailed reference viewed: 218 (13 UL)![]() ; Merkulov, Sergei ![]() in Letters in Mathematical Physics (2016), 106(9), 1199-1215 The notion of a quantizable odd Lie bialgebra is introduced. A minimal resolution of the properad governing such Lie bialgebras is constructed. Detailed reference viewed: 197 (5 UL)![]() Bollig, Sabine ![]() ![]() Book published by dohrmannVerlag (2016) Detailed reference viewed: 192 (4 UL)![]() Leist, Anja ![]() in Gerontologist (2016), 56(S3), 428-429 Detailed reference viewed: 134 (11 UL)![]() Heimböckel, Dieter ![]() ![]() in ZiG (2016), 7(1), Detailed reference viewed: 127 (5 UL)![]() ![]() ; Priem, Karin ![]() in Thyssen, Geert; Priem, Karin (Eds.) Modes and Meaning: Displays of Evidence in Education (2016) Detailed reference viewed: 130 (6 UL)![]() ![]() Priem, Karin ![]() in Thyssen, Gert; Priem, Karin (Eds.) Modes and Meaning: Displays of Evidence in Education (2016) Detailed reference viewed: 64 (3 UL)![]() Chauvel, Louis ![]() ![]() E-print/Working paper (2016) Detailed reference viewed: 209 (10 UL)![]() Hartung, Anne ![]() in Review of Income and Wealth (2016), 62 Detailed reference viewed: 109 (4 UL)![]() Chauvel, Louis ![]() ![]() in UNESCO (Ed.) World Social Science Report 2016. Challenging Inequalities: Pathways to a Just World (2016) Detailed reference viewed: 317 (27 UL)![]() ; Priem, Karin ![]() Book published by Routledge (2016) Detailed reference viewed: 151 (5 UL) |
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