![]() ![]() Hu, Adelheid ![]() in Zeitschrift für Fremdsprachenforschung (1999), 10(2), 277-303 Detailed reference viewed: 893 (3 UL)![]() Torun, Engin ![]() in Physical Review. B, Condensed Matter (2018), 97 Accurately described excitonic properties of transition metal dichalcogenide heterobilayers (HBLs) are crucial to comprehend the optical response and the charge carrier dynamics of them. Excitons in ... [more ▼] Accurately described excitonic properties of transition metal dichalcogenide heterobilayers (HBLs) are crucial to comprehend the optical response and the charge carrier dynamics of them. Excitons in multilayer systems possess an inter- or intralayer character whose spectral positions depend on their binding energy and the band alignment of the constituent single layers. In this paper, we report the electronic structure and the absorption spectra of MoS2/WS2 and MoSe2/WSe2 HBLs from first-principles calculations. We explore the spectral positions, binding energies, and the origins of inter- and intralayer excitons and compare our results with experimental observations. The absorption spectra of the systems are obtained by solving the Bethe-Salpeter equation on top of a G0W0 calculation, which corrects the independent-particle eigenvalues obtained from density-functional theory. Our calculations reveal that the lowest energy exciton in both HBLs possess an interlayer character which is decisive regarding their possible device applications. Due to the spatially separated nature of the charge carriers, the binding energy of interlayer excitons might be expected to be considerably smaller than that of intralayer ones. However, according to our calculations, the binding energy of lowest energy interlayer excitons is only ∼20% lower due to the weaker screening of the Coulomb interaction between layers of the HBLs. Therefore, it can be deduced that the spectral positions of the interlayer excitons with respect to intralayer ones are mostly determined by the band offset of the constituent single layers. By comparing oscillator strengths and thermal occupation factors, we show that in luminescence at low temperature, the interlayer exciton peak becomes dominant, while in absorption it is almost invisible. [less ▲] Detailed reference viewed: 268 (13 UL)![]() ; ; Haan, Serge ![]() in Cell Communication and Signaling (2010), 8 BACKGROUND: Interleukin (IL)-27 is a cytokine belonging to the IL-6/IL-12 cytokine family that is secreted by activated macrophages and dendritic cells and which strongly acts on T-cells and cells of the ... [more ▼] BACKGROUND: Interleukin (IL)-27 is a cytokine belonging to the IL-6/IL-12 cytokine family that is secreted by activated macrophages and dendritic cells and which strongly acts on T-cells and cells of the innate immune system. Not much is known about possible effects of IL-27 on other cell types. It signals via the common IL-6-type-cytokine receptor chain gp130 and the IL-27-specific chain WSX-1. We previously described that IL-27 also stimulates hepatoma cells and primary hepatocytes. The aim of this study was to investigate whether IL-27 would also act on hepatic stellate cells (HSC), the second most abundant hepatic cell type, which would demonstrate a more general role of this cytokine in the liver. RESULTS: Using a human HSC line and primary rat HSC we investigated the signalling characteristics of IL-27 in these cells. We show that IL-27 activates signal transducer and activator of transcription (STAT) 1 and to a minor extent STAT3 in a human HSC cell line and that it leads to the induction of STAT1 target genes such as interferon response factor-1, myxovirus resistance A and STAT1 itself. Similarly we find that IL-27 also elicits STAT1-dependent responses in primary rat HSC. CONCLUSIONS: We provide the first evidence for a function of IL-27 in HSC and show that its responses resemble Interferon-gamma-like functions in these cells. Our data suggests that IL-27 may play an important role in the context of liver inflammation by acting on the different liver cell types. [less ▲] Detailed reference viewed: 134 (4 UL)![]() ; Wiesinger, Monique ![]() in Hepatology (2009), 50(2), 585-91 Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most ... [more ▼] Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most studies, the effects of IL-27 on T cells were investigated; however, not much is known about possible effects of IL-27 on other cell types. IL-27 signals via the common IL-6-type cytokine receptor chain gp130 and the IL-27-specific chain WSX-1. Given the importance of gp130 in regulating liver responses such as the acute phase response or liver regeneration, we investigated whether IL-27 could also have a function in liver cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a sustained signal transducer and activator of transcription (STAT)1 and STAT3 activation. Whereas the STAT3 mediated responses to IL-27 (gamma-fibrinogen and hepcidin induction) are not detectable, we observe an interferon-gamma (IFN-gamma)-like STAT1 response leading to the induction of interferon-regulated proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9, myxovirus resistance A and guanylate binding protein 2. CONCLUSION: Our study provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and shows that IL-27 responses are not restricted to the classical immune cells. Our results suggest that IL-27 exerts IFN-like functions in liver cells and that it can contribute to the antiviral response in these cells. [less ▲] Detailed reference viewed: 74 (7 UL)![]() ![]() ; ; et al in Oncogene (1999), 18(25), 3742-53 Interleukin-6 (IL-6)-type cytokines lead to growth arrest of human A375 melanoma cells. The present study demonstrates that this effect depends on the activation of STAT transcription factors. We observed ... [more ▼] Interleukin-6 (IL-6)-type cytokines lead to growth arrest of human A375 melanoma cells. The present study demonstrates that this effect depends on the activation of STAT transcription factors. We observed a correlation between the extent of growth inhibition exerted by IL-6, IL-6 plus soluble IL-6 receptor or oncostatin M (OSM) and the intensities of STAT3 and STAT1 signals. A truncated chimeric receptor retaining only the membrane-proximal region of gp130, the common signal transducer of IL-6-type cytokines, did neither activate STATs nor mediate growth arrest of stable transfectants. These functions were restored by the addition of short STAT recruitment modules comprising critical tyrosine residues from gp130 (Y767, Y814). A receptor carrying tyrosine module Y759 of gp130 effectively mediated activation of the phosphatase SHP-2 but did not alter cell growth. Overexpression of dominant negative forms of STAT3 but not STAT1 abrogated the inhibitory effect of OSM and IL-6 in A375 cells. In addition, we have identified the cyclin-dependent kinase inhibitor p27/Kipl as a novel target to be regulated by IL-6-type cytokines. Stimulation-dependent upregulation of p27 mRNA occurred STAT3-dependently. Also p27 protein accumulated which coincided with the disappearance of hyperphosphorylated retinoblastoma protein in three human melanoma cell lines sensitive to IL-6-type cytokines. [less ▲] Detailed reference viewed: 112 (0 UL)![]() Minoungou, Wendkouni Nadège ![]() Doctoral thesis (2022) Hepatocellular carcinoma (HCC), the main form of primary liver cancer, is the second leading cause of cancer-related deaths worldwide after lung cancer. Multiple aetiologies have been associated with the ... [more ▼] Hepatocellular carcinoma (HCC), the main form of primary liver cancer, is the second leading cause of cancer-related deaths worldwide after lung cancer. Multiple aetiologies have been associated with the development of HCC, which arises in most cases in the context of a chronically inflamed liver. HCC is in fact an inflammation-driven cancer, with the TNF and IL6 families of cytokines playing key roles in maintaining a chronic inflammatory state, promoting hepatocarcinogenesis. IL6 signals mainly through the JAK1/STAT3 signal transduction pathway and is known to play key roles in liver physiology and disease. In the interest of identifying novel players and downstream effectors of the IL6/JAK1/STAT3 signalling pathway that may contribute to the signal transduction of IL6 in liver-derived cells, we have been investigating the expression of long non-coding RNAs (lncRNAs) in response to treatment with the designer cytokine Hyper-IL6. Indeed, lncRNAs have recently emerged as a key layer of biological regulation and have been shown to be differentially expressed in cancer, including HCC. Upon analysis of time series transcriptomics data, we have identified hundreds of lncRNAs to be differentially expressed in HepG2, HuH7, and Hep3B hepatoma cells upon cytokine stimulation; 26 of which are common to the three cell lines tested. qPCR validation experiments have been performed for several lncRNAs, such as for the liver-specific lncRNA linc-ELL2. By functionally characterising identified clusters of IL6-regulated coding and non-coding genes in hepatoma cells, we propose, based on a guilt-by-association hypothesis, novel functions for previously poorly characterized lncRNAs and pseudogenes such as AL391422.4 or TUBA5P. Several lncRNA genes seem to be co-regulated with a protein-coding gene localized in their vicinity. For example, Hyper-IL-6 increases the mRNA and protein levels of XBP1, a well-known regulator of the unfolded protein response. At the same time, the expression of lncRNA AF086143 increases, which is expressed from the same gene locus in a bidirectional way. The targeted as well as a genome-wide analysis of lncRNA/mRNA gene pairs indicates a possible cis-regulatory role of lncRNAs with regards to their antisense and bidirectional protein coding counterparts. Taken together, these results provide a comprehensive characterisation of the lncRNA and pseudogene repertoire of IL6-regulated genes in hepatoma cells. Our results emphasize lncRNAs as crucial components of the gene regulatory networks affected by cytokine signalling pathways. [less ▲] Detailed reference viewed: 49 (15 UL)![]() ![]() ; ; et al in Journal of Investigative Dermatology (2001), 117(1), 132-40 Development of cytokine resistance is an important feature of melanoma cells during tumor progression. To study the mechanisms of interleukin-6 resistance, we examined an interleukin-6 sensitive (WM35 ... [more ▼] Development of cytokine resistance is an important feature of melanoma cells during tumor progression. To study the mechanisms of interleukin-6 resistance, we examined an interleukin-6 sensitive (WM35) and an interleukin-6 unresponsive cell line (WM9). Interleukin-6 treatment resulted in rapid inhibition of cyclin-dependent kinase 2/cyclin E activity and accumulation of the hypophosphorylated retinoblastoma protein in WM35 but not in WM9 cells. In contrast to previous reports, no differences in the expression of the cyclin-dependent kinase 2 inhibitor p21Cip1/WAF1 upon interleukin-6 treatment were found in both cell lines. Interleukin-6-induced inhibition of cyclin-dependent kinase 2 was also not due to changes in protein expression of cyclin-dependent kinase 2, cyclin E, p27Kip1 and cdc25A, a phosphatase positively regulating cyclin-dependent kinase 2 activity. As it is established that interleukin-6 resistance of WM9 cells is not caused by differential interleukin-6 receptor expression, we studied whether this is due to defective interleukin-6 signaling in which activation of signal transducer and activator of transcription 3 is a critical step. WM9 cells showed reduced tyrosine phosphorylation, DNA binding, and delayed nuclear translocation of signal transducer and activator of transcription 3 as compared with WM35 cells. The kinase upstream of signal transducer and activator of transcription 3, Janus kinase 1, was constitutively tyrosine-phosphorylated in WM9 cells and did not respond to interleukin-6 with increased phosphorylation. As compared with WM35 cells, interleukin-6 treatment of WM9 cells was not paralleled by reduced activity of the mitogen-activated protein kinase kinase-1, which suppresses activation of signal transducer and activator of transcription 3. Our data suggest that resistance of advanced melanoma cells to interleukin-6 is associated with reduced inhibition of cyclin-dependent kinase 2, which appears to be a consequence of a complex alteration in interleukin-6 signal transduction. [less ▲] Detailed reference viewed: 103 (3 UL)![]() ![]() ; Behrmann, Iris ![]() in Biochemical Journal (1998), 334 (Pt 2) The family of cytokines signalling through the common receptor subunit gp130 comprises interleukin (IL)-6, IL-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1 ... [more ▼] The family of cytokines signalling through the common receptor subunit gp130 comprises interleukin (IL)-6, IL-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1. These so-called IL-6-type cytokines play an important role in the regulation of complex cellular processes such as gene activation, proliferation and differentiation. The current knowledge on the signal-transduction mechanisms of these cytokines from the plasma membrane to the nucleus is reviewed. In particular, we focus on the assembly of receptor complexes after ligand binding, the activation of receptor-associated kinases of the Janus family, and the recruitment and phosphorylation of transcription factors of the STAT family, which dimerize, translocate to the nucleus, and bind to enhancer elements of respective target genes leading to transcriptional activation. The important players in the signalling pathway, namely the cytokines and the receptor components, the Janus kinases Jak1, Jak2 and Tyk2, the signal transducers and activators of transcription STAT1 and STAT3 and the tyrosine phosphatase SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase] are introduced and their structural/functional properties are discussed. Furthermore, we review various mechanisms involved in the termination of the IL-6-type cytokine signalling, namely the action of tyrosine phosphatases, proteasome, Jak kinase inhibitors SOCS (suppressor of cytokine signalling), protein inhibitors of activated STATs (PIAS), and internalization of the cytokine receptors via gp130. Although all IL-6-type cytokines signal through the gp130/Jak/STAT pathway, the comparison of their physiological properties shows that they elicit not only similar, but also distinct, biological responses. This is reflected in the different phenotypes of IL-6-type-cytokine knock-out animals. [less ▲] Detailed reference viewed: 141 (1 UL)![]() ![]() Bréchard, Sabrina ![]() ![]() ![]() in Cell Calcium (2005), 37(6), 531-40 In response to a variety of stimuli, neutrophils release large amount of reactive oxygen species (ROS) generated by NADPH oxidase. This process known as the respiratory burst is dependent on cytosolic ... [more ▼] In response to a variety of stimuli, neutrophils release large amount of reactive oxygen species (ROS) generated by NADPH oxidase. This process known as the respiratory burst is dependent on cytosolic free calcium concentration ([Ca(2+)](i)). Proinflammatory cytokines such as interleukin-8 (IL-8) may modulate ROS generation through a priming phenomenon. The aim of this study was to determine the effect of human IL-8 on ROS production in neutrophil-like dimethylsulfoxide-differentiated HL-60 cells (not equalHL-60 cells) and further to examine the role of Ca(2+) mobilization during the priming. IL-8 at 10 nM induced no ROS production but a [Ca(2+)](i) rise (254 +/- 36 nM). IL-8 induced a strongly enhanced (2 fold) ROS release during stimulation with 1 microM of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF). This potentiation of ROS production is dependent of extracellular Ca(2+) (17.0+/-4.5 arbitrary units (A.U.) in the absence of Ca(2+) versus 56.6 +/- 3.9 A.U. in the presence of 1.25 mM of Ca(2+)). Also, IL-8 enhanced fMLF-stimulated increase in [Ca(2+)](i) (375 +/- 35 versus 245 +/- 21 nM, 0.1 microM of fMLF). IL-8 had no effect on not equalHL-60 cells in response to 1 microM of thapsigargin (472 +/- 66 versus 470 +/- 60 nM). In conclusion, Ca(2+) influx is necessary for a full induction of neutrophil priming by IL-8. [less ▲] Detailed reference viewed: 155 (2 UL)![]() Ehrhart, Sabine ![]() Presentation (2012, October 16) Detailed reference viewed: 58 (2 UL)![]() ![]() Kreis, Stephanie ![]() in Experimental Cell Research (2005), 305(1), 110-121 Integrin receptors are crucial players in cell adhesion and migration. Identification and characterization of cellular proteins that interact with their short α and β cytoplasmic tails will help to ... [more ▼] Integrin receptors are crucial players in cell adhesion and migration. Identification and characterization of cellular proteins that interact with their short α and β cytoplasmic tails will help to elucidate the molecular mechanisms by which integrins mediate bi-directional signaling across the plasma membrane. Integrin α2β1 is a major collagen receptor but to date, only few proteins have been shown to interact with the α2 cytoplasmic tail or with the α2β1 complex. In order to identify novel binding partners of a α2β1cytoplasmic domain complex, we have generated recombinant GST-fusion proteins, incorporating the leucine zipper heterodimerization cassettes of Jun and Fos. To ascertain proper functionality of the recombinant proteins, interaction with natural binding partners was tested. GST-α2 and GST-Jun α2 bound His-tagged calreticulin while GST-β1 and GST-Fos β1 proteins bound talin. In screening assays for novel binding partners, the immobilized GST-Jun α2/GST-Fos β1 heterodimeric complex, but not the single subunits, interacted specifically with endothelial cell-derived vimentin. Vimentin, an abundant intermediate filament protein, has previously been shown to co-localize with αvβ3-positive focal contacts. Here, we provide evidence that this interaction also occurs with α2β1-enriched focal adhesions and we further show that this association is lost after prolonged adhesion of endothelial cells to collagen. © 2005 Elsevier Inc. All rights reserved. [less ▲] Detailed reference viewed: 103 (5 UL)![]() Conac, Pierre-Henri ![]() ![]() Book published by Cambridge University Press (2013) Detailed reference viewed: 166 (8 UL)![]() ; ; et al in International Journal of Molecular Sciences (2011), 12(8), 4850-60 The paper presents a model for simulating the protein folding process in silico. The two-step model (which consists of the early stage-ES and the late stage-LS) is verified using two proteins, one of ... [more ▼] The paper presents a model for simulating the protein folding process in silico. The two-step model (which consists of the early stage-ES and the late stage-LS) is verified using two proteins, one of which is treated (according to experimental observations) as the early stage and the second as an example of the LS step. The early stage is based solely on backbone structural preferences, while the LS model takes into account the water environment, treated as an external hydrophobic force field and represented by a 3D Gauss function. The characteristics of 1ZTR (the ES intermediate, as compared with 1ENH, which is the LS intermediate) confirm the link between the gradual disappearance of ES characteristics in LS structural forms and the simultaneous emergence of LS properties in the 1ENH protein. Positive verification of ES and LS characteristics in these two proteins (1ZTR and 1ENH respectively) suggest potential applicability of the presented model to in silico protein folding simulations. [less ▲] Detailed reference viewed: 115 (0 UL)![]() Karimpour, Mohammad Reza ![]() Doctoral thesis (2022) In the present work, the interactions between neutral molecular systems subject to external static electric fields are studied. To comprehensively explore the effects of external fields on intermolecular ... [more ▼] In the present work, the interactions between neutral molecular systems subject to external static electric fields are studied. To comprehensively explore the effects of external fields on intermolecular interactions, the two most reliable frameworks in the subject, namely molecular quantum mechanics and quantum electrodynamics are employed while atomic and molecular responses are modeled using quantum Drude oscillators (QDO). In the first part of the work, the focus is to understand the interplay between dispersion and field-induced forces in two-body systems for both nonretarded and retarded ranges of inter-species distances. To identify the origin and the mechanism responsible for different field-induced interactions, a complementary approach based on classical electrodynamics with a zero-point radiation field, namely stochastic electrodynamics, is employed. The results show that neglecting higher-order contributions coming from field-induced hyperpolarizabilities of atoms, the dispersion interaction remains unchanged by the external uniform static field, for both regimes. However, using an external static field one can control the magnitude and characteristics of intermolecular interactions. The second part of the work is devoted to the extension of the study to many-body interacting systems. There, the total interaction energy in systems with many interacting atoms or molecules is obtained by extending the well-established theory of many-body dispersion (MBD) interactions to the presence of external static electric fields. Diagonalization of the Hamiltonian of the system in the nonretarded regime and in the framework of quantum mechanics yields the total energy of the interacting system in terms of the corresponding normal mode frequencies. Subtraction of the energy of the non-interacting QDOs-in-fields from the total energy of the interacting system results in the many-body interaction energy. The impact of the field-induced many-body contributions is investigated for a benzene dimer as well as for two carbyne chains. Varying the number of carbon atoms per chain demonstrates the significance of the field-induced many-body terms in the interplay between dispersion and field-induced interactions. Such contributions can be of great importance for controlling delamination and self-assembly of materials in static electric fields. [less ▲] Detailed reference viewed: 137 (23 UL)![]() Cebotari, Victor ![]() in Children and Youth Services Review (2021), 121(February), 105821 Relatively little is known about the effects of parental migration on the living conditions of children who stay behind. Using survey data collected in 2010 from Ghanaian school children (11–18 years; N ... [more ▼] Relatively little is known about the effects of parental migration on the living conditions of children who stay behind. Using survey data collected in 2010 from Ghanaian school children (11–18 years; N = 2100), this study investigates variations in children’s durable goods and private utilities when parents migrate internally or internationally compared to a control group of children who live with their parents. The study also investigates whether the effects are contingent upon the marital situation of the parents. The findings show that parental migration is not associated with poorer living conditions for Ghanaian children. Rather, specific factors, such as parental divorce, internal migration and the gender of the child, influence whether children experience a decline in their living conditions when parents migrate. [less ▲] Detailed reference viewed: 78 (2 UL)![]() Sneessens, Henri ![]() in Louvain Economic Review - Recherches Economiques de Louvain (1996), 62(2-3), 255-86 Detailed reference viewed: 43 (1 UL)![]() Hofmann, Herwig ![]() in Bradley, Kieran; Travers, Noel; Whelan, Anthony (Eds.) Of Courts and Constitutions (2014) This paper explores the diversifying limits to integration by harmonisation of national law for the ‘establishment and functioning of the internal market’ (Article 114 TFEU) by the adoption of substantive ... [more ▼] This paper explores the diversifying limits to integration by harmonisation of national law for the ‘establishment and functioning of the internal market’ (Article 114 TFEU) by the adoption of substantive and procedural ‘measures’ under EU law in the past decade and a half – all the way to the CJEU’s ruling regarding ESMA powers in Short Selling. [less ▲] Detailed reference viewed: 130 (4 UL)![]() ; ; Anton, Fernand ![]() Poster (2009) Detailed reference viewed: 107 (0 UL)![]() ; ; Anton, Fernand ![]() in European Journal of Pain (2011), 15(1), 45-52 Detailed reference viewed: 70 (2 UL)![]() Aucher, Guillaume ![]() in Studia Logica (2010), 94(1), 1-22 Representing an epistemic situation involving several agents obviously depends on the modeling point of view one takes. We start by identifying the types of modeling points of view which are logically ... [more ▼] Representing an epistemic situation involving several agents obviously depends on the modeling point of view one takes. We start by identifying the types of modeling points of view which are logically possible. We call the one traditionally followed by epistemic logic the perfect external approach, because there the modeler is assumed to be an omniscient and external observer of the epistemic situation. In the rest of the paper we focus on what we call the internal approach, where the modeler is one of the agents involved in the situation. For this approach we propose and axiomatize a logical formalism based on epistemic logic. This leads us to formalize some intuitions about the internal approach and about its connections with the external ones. Finally, we show that our internal logic is decidable and PSPACE-complete. [less ▲] Detailed reference viewed: 130 (0 UL) |
||