582 research outputs found

    Conspiracies beyond Fake News : Produsing Reinformation on Presidential Elections in the Transnational Hybrid Media System

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    Among work published between January 2018 and December 2019 in Sociological Inquiry, "Conspiracies beyond Fake News. Produsing Reinformation on Presidential Elections in the Transnational Hybrid Media System" is among the top 10% most downloaded papers.As presidential elections carry the promise of distilling the contested and elusive 'will of the people', the protracted media event intensifies the public demand for exposing the transgressions of the aspiring political elite. This expectation provides fertile ground for investigative journalism, ultrapartisan smear campaigns, fake news, and full-fledged conspiracy theories that are sometimes difficult to differentiate from one another in a hybridized media space. We compare three unique conspiracy stories - Macronleaks, Pizzagate, and Voter fraud - emerging during the previous French and American elections. We assess the divergent strategies of social action that contribute to the stories' dissimilar patterns for intervening the political news cycle with the 'reinformative toolkit' and deconstruct the common conspiratorial 'masterplot' for 'reinforming' the public. Focusing on online 'produsers' - media users functioning as (dis)information producers - we analyze how the grassroots level participated in shaping the conspiracy stories' synopses and channeling news-framed, conspiratory content between mainstream and 'countermedia' outlets.Peer reviewe

    In Search for Unexpected Allies? Radical Right Remediation of ‘the 2015 Refugee Crisis’ on Social Media

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    This chapter analyses the remediation of the mainstream news cycle on the ‘refugee crisis’ to the social media audiences of two Finnish anti-immigration groups, namely ‘Close the Borders!’ and ‘Finland First’. The analysis focuses on the post-truth tropes employed by these groups as practices for subverting information and interpretations originally sourced to epistemic authorities. In doing so, the chapter provides a more nuanced approach to the post-truth tropes where the generation of ‘fake news’ and explicit disinformation is only the tip of the iceberg. The results show that by harnessing careful and context-sensitive remediation practices, the radical right is effectively able to hijack the news cycle with the alleged support from ‘unlikely allies’ among epistemic authorities.Peer reviewe

    Mediating shame and pride : countermedia coverage of Independence Day in Poland and the US

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    This article adopts a comparative qualitative approach to studying the rhetoric of injured pride in the coverage of Independence Day celebrations by the right-wing countermedia in Poland (wPolityce.pl) and the US (Breitbart News) from 2012 to 2018. In both countries, the number of countermedia articles on Independence Day proliferated in the aftermath of the election of the Law and Justice party (2015) and Donald Trump (2016). Based on the analysis of the narrative strategy for affective polarisation, we argue that the countermedia mobilise support from an electorate of ‘the disenfranchised’ by strategically invoking emotions of shame and pride. By positioning the radical right as a political force that shields ‘patriots’ from the leftist ‘pedagogy of shame’, the outlets instrumentalise the mobilising potential of shame by transforming it into righteous anger and pride. This strategy results in a mediated ‘emotional regime’ that offers guidelines for an acceptable emotional repertoire for the members of the nationally bound in-group.Peer reviewe

    Allium compounds, dipropyl and dimethyl thiosulfinates, as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines: Antiproliferative effects of thiosulfinates

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    There is increasing evidence that certain Allium derivatives have beneficial effects on coronary diseases and cancer. Thus, thiosulfinates have already been shown to inhibit platelet aggregation and clot retraction. Here, we have examined the effects of dipropyl and dimethyl thiosulfinates against acute myeloid leukemia (AML) cell lines. Both thiosulfinates inhibited proliferation of cell lines in a concentation-dependent fashion without inducing necrosis. Moreover, they inhibited the expression of matrix metalloproteinase-9 (MMP-9) protein and its gelatinolytic activity. The mechanisms by which these molecules inhibit MMP9 are now studied using the RT-PCR approach. In parallel, the effects of the related molecules dipropyl and dimethyldisulfides are being evaluated. Already, our data highlight the potential application of such molecules to cancer control.International audienceEpidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All2TS), dipropyl TS (Pr2TS) and dimethyl TS (Me2TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-? protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cel lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML

    Functional characterization of two M42 aminopeptidases erroneously annotated as cellulases

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    Several aminopeptidases of the M42 family have been described as tetrahedral-shaped dodecameric (TET) aminopeptidases. A current hypothesis suggests that these enzymes are involved, along with the tricorn peptidase, in degrading peptides produced by the proteasome. Yet the M42 family remains ill defined, as some members have been annotated as cellulases because of their homology with CelM, formerly described as an endoglucanase of Clostridium thermocellum. Here we describe the catalytic functions and substrate profiles CelM and of TmPep1050, the latter having been annotated as an endoglucanase of Thermotoga maritima. Both enzymes were shown to catalyze hydrolysis of nonpolar aliphatic L-amino acid-pNA substrates, the L-leucine derivative appearing as the best substrate. No significant endoglucanase activity was measured, either for TmPep1050 or CelM. Addition of cobalt ions enhanced the activity of both enzymes significantly, while both the chelating agent EDTA and bestatin, a specific inhibitor of metalloaminopeptidases, proved inhibitory. Our results strongly suggest that one should avoid annotating members of the M42 aminopeptidase family as cellulases. In an updated assessment of the distribution of M42 aminopeptidases, we found TET aminopeptidases to be distributed widely amongst archaea and bacteria. We additionally observed that several phyla lack both TET and tricorn. This suggests that other complexes may act downstream from the proteasome

    Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

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    Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All2TS), dipropyl TS (Pr2TS) and dimethyl TS (Me2TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML

    Counter-media entice with a promise to expose the lies of those in power

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    Valeuutisista puhutaan kaikkialla, mutta onko valeuutisissa todella kyse valheista? Eri maissa toimivat vastamediat keskittyvÀt ennen kaikkea kehystÀmÀÀn uutistapahtumat uudella tavalla ja esittÀmÀÀn itsensÀ perinteisen uutismedian piilottamien totuuksien paljastajana

    Identification de nouvelles cibles pro-apoptotiques dans les leucémies aiguës myéloblastiques

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    Les leucĂ©mies aiguĂ«s myĂ©loblastiques (LAM) sont des maladies hĂ©matopoĂŻĂ©tiques caractĂ©risĂ©es par une prolifĂ©ration incontrĂŽlĂ©e de prĂ©curseurs myĂ©loĂŻdes bloquĂ©s Ă  divers stades de diffĂ©renciation. Le pronostic des LAM reste sombre Ă  cause de la rĂ©sistance aux traitements et des rechutes aprĂšs rĂ©mission. En consĂ©quence, des thĂ©rapies moins intensives et mieux tolĂ©rĂ©es doivent ĂȘtre dĂ©veloppĂ©es ; ceci nĂ©cessite le dĂ©veloppement de stratĂ©gies combinatoires associant des molĂ©cules avec des modes d action diffĂ©rents pour augmenter l efficacitĂ© des traitements. Plusieurs approches sont en cours d Ă©tude prĂ©clinique et clinique [inhibiteurs des voies de signalisation PI3K/Akt/mTOR, anticorps monoclonaux couplĂ©s Ă  une drogue (MylotargÂź), inhibiteurs du protĂ©asome (bortezomib) ] Des travaux rĂ©cents ont relancĂ© l intĂ©rĂȘt de l Ă©tude des molĂ©cules d origine naturelle pour le traitement des cancers. Ainsi, l acide flavone-8-acĂ©tique (FAA) a suscitĂ© de nombreux espoirs au vu de son action sur les tumeurs greffĂ©es chez la souris ; il s est nĂ©anmoins rĂ©vĂ©lĂ© inactif chez l homme du fait d une mĂ©tabolisation diffĂ©rente de celle de la souris. L objectif de ma thĂšse a Ă©tĂ© d Ă©tudier les effets d anticorps monoclonaux dirigĂ©s contre l antigĂšne tumoral CD13 (aminopeptidase-N) et de deux dĂ©rivĂ©s de FAA, la 2 ,3-Dinitroflavone-8-acĂ©tique (DNFAA ; inhibiteur de l activitĂ© enzymatique de CD13) et la 3,3 -Diamino-4 -mĂ©thoxyflavone (DD1) dans les LAM. Mon Ă©tude a montrĂ© que DNFAA n affecte ni la prolifĂ©ration ni la survie des cellules de LAM (lignĂ©es et cellules primaires). Cependant, le traitement de ces cellules par les anticorps anti-CD13, (MY7, SJ1D1, WM15 ; reconnaissant ou non le site enzymatique) induit l apoptose en activant les voies extrinsĂšque et intrinsĂšque. Dans la voie intrinsĂšque, les anti-CD13 rĂ©gulent nĂ©gativement l expression des protĂ©ines anti-apoptotiques Bcl-2 et Mcl-1 et positivement l expression de la protĂ©ine pro-apoptotique Bax. De plus, l activation de la voie PI3K/Akt apparaĂźt associĂ©e au processus apoptotique. Mon Ă©tude sur les effets du 3,3 -Diamino-4 -mĂ©thoxyflavone dans les cellules de LAM montre une induction d apoptose rĂ©sultant de la convergence de l inhibition du protĂ©asome et de l activation des voies extrinsĂšque et intrinsĂšque. Les cibles de DD1 sont le protĂ©asome, la kinase p70S6K (kinase en aval de mTOR), et les protĂ©ines pro-apoptotiques Bad et Bax. De plus, j ai mis en Ă©vidence la dĂ©gradation de p70S6K sous l action de la caspase 3, par le traitement avec DD1, nouvelle propriĂ©tĂ© partagĂ©e par DD1 et le bortezomib. En conclusion, mon travail a permis de mettre en Ă©vidence les capacitĂ©s Ă  induire in vitro des voies d apoptose dĂ©ficientes dans les cellules de LAM, d anticorps monoclonaux anti-CD13 et de la flavone originale, 3,3 -Diamino-4 -methoxyflavone, en tant que nouvel inhibiteur du protĂ©asome. Les propriĂ©tĂ©s de ces agents pro-apoptotiques mĂ©ritent d ĂȘtre analysĂ©es de façon plus approfondie.Acute Myeloid Leukaemia (AML) is a deadly disease characterized by the clonal expansion and accumulation of hematopoietic stem cells arrested at various stages of development. Clinical research efforts are currently focusing on targeted therapies that induce apoptosis in AML cells such as PI3K/Akt/mTOR pathway inhibitors, monoclonal antibodies (MylotargÂź), proteasome inhibitor (bortezomib) Natural products such as flavonoids have been reported as anticancer agents due to their antioxidant properties as well as to their possible interactions with signalling cascades. Therefore, flavone-8-acetic acid (FAA) has raised considerable attention since the discovery of its exceptional activity on several murine solid tumours. Unfortunately, these promising properties were not confirmed on human due to differential metabolization between human and mouse. The aim of my PhD was to study effects of monoclonal antibody against aminopeptide-N/CD13 and FAA derivatives, 2 ,3-Dinitroflavone-8-acetic (DNFAA ; APN/CD13 inhibitor) and 3,3 -Diamino-4 -methoxyflavone (DD1) on acute myeloid leukaemia cells. My studies have shown that DNFAA does not modify proliferation or survival of LAM primary and cell lines. However, treatment of these cells by CD13 antibodies (MY7, SJ1D1 and WM15) induces apoptosis by triggering extrinsic and intrinsic apoptotic pathways. Regarding the intrinsic pathway, anti-CD13 down-regulate anti-apoptotic proteins Bcl-2 and Mcl-1 and up-regulate the pro-apoptotic protein Bax. Morever, PI3K/Akt signalling pathway seems to be associated with this apoptosis. My study about 3,3 -Diamino-4 -methoxyflavone effects on LAM cells has shown that DD1 induces apoptosis by proteasome inhibition and intrinsic and extrinsic pathways induction. DD1 targets p70S6 kinase (a downstream kinase of mTOR) and pro-apoptotic proteins Bad and Bax. Moreover, I have shown p70S6K degradation by caspase 3 during DD1 treatment, a new characteristic shared by DD1 and Bortezomib. As a conclusion, my works demonstrated that CD13 antibodies and a new synthetic flavone are able to induce apoptosis signalling pathway normally impaired on AML cells. Characteristics of these agents deserve to be more deeply analyzed.PARIS5-Bibliotheque electronique (751069902) / SudocPARIS-BIUM-Bib. Ă©lectronique (751069903) / SudocSudocFranceF

    Crystal structure of the cold-active aminopeptidase from Colwellia psychrerythraea, a close structural homologue of the human bifunctional leukotriene A4 hydrolase

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    peer reviewedThe crystal structure of a cold-active aminopeptidase (ColAP) from Colwellia psychrerythraea strain 34H has been determined, extending the number of crystal structures of the M1 metallopeptidase family to four among the 436 members currently identified. In agreement with their sequence similarity, the overall structure of ColAP displayed a high correspondence with leukotriene A4 hydrolase (LTA4H), a human bifunctional enzyme that converts leukotriene A4 (LTA4) in the potent chemoattractant leukotriene B4. Indeed, both enzymes are composed of three domains, an N-terminal saddle-like domain, a catalytic thermolysin-like domain, and a less conserved C-terminal alpha-helical flat spiral domain. Together, these domains form a deep cavity harboring the zinc binding site formed by residues included in the conserved HEXXHX(18)H motif. A detailed structural comparison of these enzymes revealed several plausible determinants of ColAP cold adaptation. The main differences involve specific amino acid substitutions, loop content and solvent exposure, complexity and distribution of ion pairs, and differential domain flexibilities. Such elements may act synergistically to allow conformational flexibility needed for an efficient catalysis in cold environments. Furthermore, the region of ColAP corresponding to the aminopeptidase active site of LTA4H is much more conserved than the suggested LTA4 substrate binding region. This observation supports the hypothesis that this region of the LTA4H active site has evolved in order to fit the lipidic substrate

    Politicization of migration in the countermedia style : A computational and qualitative analysis of populist discourse

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    Countermedia are ultrapartisan media outlets that position themselves in opposition to the mainstream media and ‘the establishment’. In this article, we analyse the countermedia style and its adoption by parliamentarians, particularly in the politicization of migration, in the case of Finland. We conduct an analysis of large datasets of text from Finnish countermedia, mainstream media and parliamentary speeches from 2015 to 2017, based on computationally comparing relative frequencies of n-grams, or word sequences, and a collaborative, inductive, and reflexive qualitative interpretation. We identify and describe the countermedia style – framing immigration-related news events through crisis and threat – in the countermedia itself as well as in Parliament, where we find that it is used predominantly by the right-wing populist Finns Party. We argue that rather than adopting the style ‘as is’, politicians employ a ‘politician’s filter’ to balance between representing ‘the people’ of populism and appearing as respectable politicians. The article highlights the importance of studying new forms of online alternative media which can be used to politicize issues in the public sphere, particularly using populist styles. Keywords: alternative media, countermedia, immigration, populism, right-wing populism, migration, online mediaPeer reviewe
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