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Pml loss worsens NEK1-linked ALS and Pml induction drives NEK1 degradation, precluding disease onset
No full textGerminal mono-allelic loss-of-function mutations of NEK1 drive Amyotrophic Lateral Sclerosis (ALS) at variable penetrance, presumably through haploinsufficiency. Modeling the ALS-associated Arg812Ter mutation in mice revealed that the resulting truncated Nek1 (Nek1 t ) is aggregation-prone, particularly in alpha-motoneurons (αMNs), and drives canonical ALS symptoms when bi-allelically expressed ( Nek1 t/t ) . Promyelocytic leukemia ( Pml ) ablation allows for ALS symptoms to occur even in heterozygote Nek1 wt/t animals, mimicking the human situation. Pml precludes disease occurrence by promoting SUMO-facilitated degradation of Nek1 t proteins through PML nuclear bodies (NBs). Conversely, Pml induction, achieved by activating the interferon pathway via poly(I:C) treatment, clears Nek1 t aggregates in αMNs, dramatically reducing ALS-associated symptoms and extending survival by 5 months. Our studies highlight the role of NEK1 aggregates in ALS pathogenesis and identifies activation of interferon pathways as a candidate therapeutic strategy that not only promotes Pml- triggered SUMOylation/degradation of toxic misfolded proteins in vivo , but also facilitates the clearance of protein aggregates, yielding dramatic clinical improvement. These observations validate PML as a relevant therapeutic target in neurodegenerative conditions associated with protein aggregation
Emergence of a Landau Level Structure in Dark Optical Lattices
No full textInternational audienceAn optical flux lattice is a set of light beams that couple different internal states of an atom, thereby producing topological energy bands. Here we present a configuration in which the atoms exhibit a dark state, i.e., an internal state that is not coupled to the light. At large light intensity, the low-energy dynamics is restricted to the dark state, leading to an effective continuum model with a Landau-level-like structure. This structure is dramatically different from that of usual topological optical lattices, which lead to discrete models in the tight-binding limit. For well-chosen atomic species, the proposed system is essentially immune to heating due to photon scattering, making it a highly promising way to emulate the integer or fractional quantum Hall effect
Proteomics-based characterization of ribosome heterogeneity in adult mouse organs
No full textInternational audienceThe translation process, leading to protein synthesis from mRNA, has been long thought to be invariable in all cellular organisms. Increasing evidence shows that it is finely regulated by variable features of the translation machinery. Notably, ribosomes, the functional units of protein synthesis, are suggested to display variations in their composition, depending on the developmental stage, cell type or physio-pathological context, thus hinting a new level of actionable regulation of gene expression. Yet, a comprehensive map of the heterogeneity of ribosome composition in ribosomal proteins (RPs) in different organs and tissues is not available. In this work, we explored tissue-specific ribosome heterogeneity using mass spectrometry-based quantitative proteomic characterization of ribosomal fractions purified from 14 adult mouse organs and tissues. We performed crossed clustering and statistical analyses of RP composition to highlight stable, variable and tissue-specific RPs across organs and tissues. Focusing on specific RPs, we validated their varying abundances using a targeted proteomic approach and western blot analyses, providing further insights into the tissue-specific ribosome RP signature. Finally, we investigated the origin of RP variations in ribosome fraction of the different tissues, by comparing RP relative amounts in our ribosomal proteomic dataset with their corresponding transcript abundances in three independent transcriptomic datasets. Interestingly, we found that, in some tissues, the RP abundance in purified ribosomes does not always correlate with the corresponding RP transcript level, arguing for a translational regulation of RP expression, and/or a regulated incorporation of RPs into ribosomes. Altogether, our data support the notion of a tissue-specific RP signature of ribosomes, which opens avenues to study how specific ribosomal composition provides an additional level of regulation to control gene expression in different tissues and organ
Los Wayana en la ciberselva. Restitución colaborativa y archivo digital en la Guayana Francesa
No full textInternational audienceThis paper examines the ethical, intellectual, and practical issues surrounding a collaborative digital restitution project known by the acronym SAWA (Savoirs autochtones wayana-apalaï). SAWA’s main objective is cultural valorization and revitalization, notably by giving the Amerindian populations of French Guyana easier access to audiovisual and photographic archives, as well as to collections of objects representative of their culture. The project is carried out in active collaboration with Amerindian experts who regularly travel to metropolitan France to work on the portal (the principal restitution tool), making decisions regarding its conception and design, as well as rights of access to audio and audiovisual data, and to study recordings and objects related to a significant but highly endangered collective ritual (marake in French, in Wayana: eputop). Finally, SAWA includes an epistemological component, reflecting on indigenous control of the archives concerning them, on the practices of collaborativerestitution, and on their incidence on the transmission of knowledge and know-how.ResumenEste artículo examina las cuestiones éticas, intelectuales y prácticas en torno a un proyecto colaborativo de restitución digital: SAWA [Savoirs autochtones wayana-apalaï]. SAWA tiene como objetivo principal la (re)vitalización cultural, en particular facilitando el acceso de las poblaciones amerindias wayana y apalaï de la Guayana Francesa, a un conjunto de colecciones audiovisuales, fotográficas y de objetos museográficos representativos de su cultura. El proyecto se lleva a cabo en colaboración activa con expertos amerindios que viajaron regularmente a Francia metropolitana, para participar en el diseño del portal digital (principal herramienta de restitución), la definición de las formas y condiciones de acceso a las colecciones sonoras y audiovisuales, así como en el estudio de las grabaciones y objetos relativos a un importante ritual colectivo en peligro de desaparición (marake en francés, eputop en wayana). Por último, SAWA incluye un análisis reflexivo y epistemológico sobre la experiencia de las poblaciones originarias que asumen el control de los fondos que les conciernen, las prácticas colaborativas de restitución y su impacto en la transmisión de conocimientos y saberes.</p
L’héritage d’Alexandre conquérant des extrémités du monde. De l’Asie Centrale au Tibet et aux musées japonais
No full textInternational audienceEn 1932 et 1933 Joseph Hackin, conservateur en chef du Musée Guimet et directeur de fait de la Délégation Archéologique Française en Afghanistan, donnait à la Maison Franco-Japonaise dont il venait d’assumer la direction une série de conférences sur le programme de l’archéologie française en Afghanistan. La quête de l’héritage de l’expédition d’Alexandre était au premier plan des préoccupations de la DAFA. Elle ne pouvait encore mettre à son actif que les découvertes spectaculaires sur l'art gréco-bouddhiques (ce n'est qu'à partir de 1964 qu'une cité grecque, Aï Khanoum, allait être fouillée).Aujourd’hui, une série de nouvelles découvertes et surtout des réinterprétations de trouvailles anciennes permettent de mieux suivre la destinée d’Alexandre le Grand comme figure mémorielle. S’il est bien connu que son culte héroïque subsiste jusqu’au début de l’époque byzantine en Occident et que son Roman a été le second best-seller du monde (après la Bible), nous pouvons démontrer maintenant que son souvenir se prolonge jusqu’au VIe siècle également sur des objets fabriqués en Asie centrale. Cette présence d’Alexandre dans les cultures iraniennes de l’Est n’est guère étonnante, si l’on pense que son image persiste jusqu'à aujourd'hui dans la mémoire littéraire du monde persanophone.Lors de cette conférence, seront notamment présentés :- Une série de têtes de terre cuite de Samarkand à l’effigie d’Alexandre, produites uniquement sur ce site dont Alexandre était au Moyen Âge réputé être le fondateur ;- Un bol d’argent découvert en Russie (kraï de Perm, à Vereino), maintenant à l’Ermitage, sans doute fabriqué en Bactriane au IVe s., figurant l’épisode historique d'Alexandre chassant le tigre près de Samarkand ; - Un bol d’argent dit de Lhassa, acquis en 1961 auprès d’une famille d’émigrés tibétains, figurant une version juive de la découverte par Alexandre de l’arbre à encens dans le sanctuaire du Soleil et de la Lune et de la fontaine d’immortalité, les deux situés aux limites orientales du monde. Le thème de cet objet comme son destin ultérieur illustrent parfaitement l’ubiquité et la plasticité de la mémoire d’Alexandre : d’abord signalé à Lhassa (où il avait peut-être abouti au IXe s. par le réseau des marchands juifs « Rhadanites »), il arrive au XXe siècle en Angleterre (à l’Ashmolean Museum d’Oxford), et se trouve maintenant exposé au Musée d’Art Oriental de Tokyo
Compte-rendu / Luxi et Erkin Azat, "Erkin Azat, lanceur d'alerte sur les camps ouïghours", Delcourt, « Encrage »
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The ‘Dawn’, the First Philanthropic Association of Muslim Women in Sarajevo, Bosnia and Herzegovina, 1919
No full textInternational audienceThis document presents a post-First World War Sarajevo middle-class Muslim women’s initiative to enhance the living conditions of impoverished Muslim women. They proposed the establishment of secular literacy courses and sewing and embroidery workshops
Marie-Hélène Blanchet, Frédéric Gabriel, Laurent Tatarenko, Autocéphalies. L’exercice de l’indépendance dans les Églises slaves orientales
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The Dead god
No full textInternational audienceA forgotten seal documents the only representation of a dead god in the arms of the god who killed him. This violent representation can be read on various level. At the simplest, it is adivine battle that finds echoes in Mesopotamian cosmogony. At a more complex level, it is about the advent of a newage that coicides with the death of the god and the subjugation of men and is garanteed by Shamash. But the seal also alludes to the birth of a new political epoch desired by the Akkadian dynasty. Lastly, the seal has a clear apotropaic value, which results from the choice of the natural colours of the stone for the different subjects: for the dead god, the seal cutter used the black vein of the stone, for the other subjects he used the white vein