IL-26 inhibits hepatitis C virus replication in hepatocytes

Publisher Copyright: © 2021 European Association for the Study of the LiverBackground & Aims: Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3+ lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV. Based on this observation and possible interactions between IL-26 and nucleic acids, we investigated the possibility that IL-26 controlled HCV infection independently of the immune system. Methods: We evaluated the ability of IL-26 to interfere with HCV replication in hepatocytes and investigated the mechanisms by which IL-26 exerts its antiviral activity. Results: We showed that IL-26 penetrated HCV-infected hepatocytes, where it interacted directly with HCV double-stranded RNA replication intermediates, thereby inhibiting viral replication. IL-26 interfered with viral RNA-dependent RNA polymerase activity, preventing the de novo synthesis of viral genomic single-stranded RNA. Conclusions: These findings reveal a new role for IL-26 in direct protection against HCV infection, independently of the immune system, and increase our understanding of the antiviral defense mechanisms controlling HCV infection. Future studies should evaluate the possible use of IL-26 for treating other chronic disorders caused by RNA viruses, for which few treatments are currently available, or emerging RNA viruses. Lay summary: This study sheds new light on the body's arsenal for controlling hepatitis C virus (HCV) infection and identifies interleukin-26 (IL-26) as an antiviral molecule capable of blocking HCV replication. IL-26, which has unique biochemical and structural characteristics, penetrates infected hepatocytes and interacts directly with viral RNA, thereby blocking viral replication. IL-26 is, therefore, a new player in antiviral defenses, operating independently of the immune system. It is of considerable potential interest for treating HCV infection and other chronic disorders caused by RNA viruses for which few treatments are currently available, and for combating emerging RNA viruses.Peer reviewe

Beyond the Right to the City: territorial autogestion and the Take over the City movement in 1970s Italy

The cry and demand for the Right to the City (RttC) risks becoming a cliché, merely signifying urban rebellion rather than proving its practical content on the ground. I explore the limits of the thesis via its fraught entanglement with private property rights and the state-form; and through Lefebvre's radical critique of the state, political economy and rights elsewhere. Rights claims, I contend, unintentionally reify the uneven power relations they aim to overcome, while routinely cauterising the hard-fought collective social force that forces social gains. As a counter to the RttC thesis, I explore the autonomous Take over the City (TotC) movements of 1970s Italy, arguing that these largely neglected eminently immanent forms of territorial community activism, brought here into dialogue with Lefebvre's conception of territorial autogestion, surpassed the RttC thesis in praxis. The experience of “Laboratory Italy” thus provides highly suggestive lessons for a contemporary politics of urban space

Against reactionary populism: Towards a new public archaeology

[EN] From Brazil to the United Kingdom, 2016 was a critical year in global politics. The panorama changed so dramatically and so fast, that it will surely have a long-lasting impact in archaeology, anthropology and related fields. Heritage, ethics and the way we relate to the public will all be affected in one way or another. In this article we reflect critically on the phenomenon of reactionary populism and how it affects the practice and theory of archaeology. There are three main lessons that can be drawn from the advance of reactionary populism across the world. First, we have learnt that mere and more liberalism is not enough to face this political phenomenon. Second, archaeologists are perhaps not as fearsome agents of Empire as we thought. And third, there were other marginalized collectives out there who were not self-assertive indigenous communities, liberal African-Americans, class-conscious industrial workers or homeless interested in documenting their lives. Based on such lessons, three things we can do: we need an archaeology that provokes the People, instead of flattering them; we need an archaeology that teaches, we need a critical and transformative pedagogy that teaches about archaeology but also uses archaeology to teach; and we do not need to go against heritage; rather, we need an archaeology that escapes the 'heritage crusade'. To conclude, we have to make archaeology political again. We must stop flirting with progressive neoliberalism and go beyond those issues of identity, ethics and narrative that have occupied the political imagination of archaeology for three decades. We need to go back to the hard core of politics—radical dissent, conflict, inequality—and reconstruct archaeology as a public engaged practice to make it a truly critical voice in the global stage.[ES] Desde Brasil al Reino Unido, el 2016 fue un año crítico en la política mundial. Todo el panorama cambió de forma tan dramática y rápida, que seguramente tendrá un largo impacto en la arqueología, antropología y disciplinas relacionadas. El patrimonio, nuestra ética profesional y la forma cómo nos relacionamos con el público, serán afectados de un modo u otro. En este texto reflexionamos críticamente sobre el populismo reaccionario y cómo éste afecta la práctica y teoría de la arqueología. Hay tres lecciones que podemos derivar del avance el populismo reaccionario en el mundo. Primero, hemos aprendido que el simple liberalismo no es suficiente para enfrentar este fenómeno político. Segundo, los profesionales de la arqueología no somos seguramente agentes tan temibles del Imperio como a menudo hemos pensado. Y tercero, hay otros colectivos marginalizados ahí fuera que no son resueltas comunidades indígenas, Afro-Americanos liberales, trabajadores industriales con conciencia de clase, o vagabundos interesados en documentar sus vivas. A partir de estas lecciones, creemos que podemos hacer tres cosas: necesitamos una arqueología que provoque al Pueblo, en vez de adularlo; necesitamos una arqueología que enseñe, necesitamos una pedagogía crítica y transformativa que enseñe sobre la arqueología, pero que además utilice la arqueología para enseñar; y no necesitamos ir contra el patrimonio, sino más bien necesitamos una arqueología que evite la “cruzada patrimonial”. La consecuencia es que debemos repolitizar de nuevo la arqueología. Debemos dejar de intercambiar saliva con el progresismo neoliberal e ir más allá de temas tópicos, como la identidad, la ética y la narrativa, que han ocupado la imaginería política de la arqueología durante treinta años. En cambio necesitamos volver al núcleo central de la política (el disentimiento, los conflictos, la desigualdad radicales) y reconstruir la arqueología como una práctica alineada con lo público para convertirla en una voz realmente crítica en el escenario global.N

Recent advances in the molecular and genetic understanding of congenital gastrointestinal malformations

Major developmental paradigms are highly conserved among vertebrates. The contribution of developmental biology to the understanding of human disease and regeneration has soared recently. We review advances in the molecular and genetic understanding of gastrointestinal development using evidence from both mammalian and nonmammalian models. When appropriate, we highlight relevance and applicability to human disease

Non-Small-Cell Lung Cancer-Sensitive Detection of the p.Thr790Met EGFR Alteration by Preamplification before PNA-Mediated PCR Clamping and Pyrosequencing

International audienceTargeted therapies and, more precisely, EGFR tyrosine kinase inhibitors (TKIs) have been a major improvement in the therapeutic management of EGFR-mutated non-small-cell lung cancers (NSCLCs). Earlier administration of these TKIs throughout tumor progression is imperative to improve patient outcomes. Consequently, studies have focused on refining the characterization of biomarkers, especially concerning the resistance mutation p.Thr790Met of EGFR. Herein, we developed peptide nucleic acid (PNA)-mediated PCR clamping followed by pyrosequencing, favoring enrichment of the mutated fraction. A preamplification step was first added to increase the amplifiable DNA fraction. Throughout the application of our method on DNA extracted from FFPE samples of 46 patients with NSCLC who had relapsed under first-generation EGFR TKI, we evaluated a sensitivity of 93.3% and a specificity of 100%. All 19 patients who were positive for the p.Thr790Met mutation with NGS were also found to be positive with our protocol. The only discordant case was a sample with no mutation detected with NGS, but which was positive with PNA. This protocol allows for the detection of the p.Thr790Met mutation with a sensitivity of 0.5% which will permit earlier detection and an improvement of therapeutic management

Outils de monitoring per-opératoire dans la chirurgie de l'oreille moyenne

L'objectif de ce projet est de déterminer les propriétés de transmission de la chaîne ossiculaire de l'oreille moyenne durant une opération chirurgicale, sans en affecter le comportement

Automobile wheel clearance estimation using magnetism

International audienceWith development and miniaturization of magnetic sensors for several years, it is now possible to imagine new applications using magnetic measures for monitoring and diagnostics. In this article this new way of research and development is presented with a concrete example concerning monitoring of wheels in an automobile.Our approach consists in using the low magnetic field created by the metallic elements of the wheel in order to localize them with low-cost high-sensitivity miniature magnetic sensors. The measures are made via a sensor network set up on a vehicle around the wheel. Then we use a physical model of the wheel in order to interpret the signals we get from the sensors. This method shows the interest of the magnetic measurement for monitoring in automobile.In this paper we present the magnetic signal created by a wheel, the mechanical model of the wheel and we present how we use them for an application: the real-time estimation of the distance between wheels and chassis (wheel clearance)

Impact of Rhamnolipids (RLs), Natural Defense Elicitors, on Shoot and Root Proteomes of Brassica napus by a Tandem Mass Tags (TMTs) Labeling Approach

International audienceThe rapeseed crop is susceptible to many pathogens such as parasitic plants or fungi attacking aerial or root parts. Conventional plant protection products, used intensively in agriculture, have a negative impact on the environment as well as on human health. There is therefore a growing demand for the development of more planet-friendly alternative protection methods such as biocontrol compounds. Natural rhamnolipids (RLs) can be used as elicitors of plant defense mechanisms. These glycolipids, from bacteria secretome, are biodegradable, non-toxic and are known for their stimulating and protective effects, in particular on rapeseed against filamentous fungi. Characterizing the organ responsiveness to defense-stimulating compounds such as RLs is missing. This analysis is crucial in the frame of optimizing the effectiveness of RLs against various diseases. A Tandem Mass Tags (TMT) labeling of the proteins extracted from the shoots and roots of rapeseed has been performed and showed a differential pattern of protein abundance between them. Quantitative proteomic analysis highlighted the differential accumulation of parietal and cytoplasmic defense or stress proteins in response to RL treatments with a clear effect of the type of application (foliar spraying or root absorption). These results must be considered for further use of RLs to fight specific rapeseed pathogens