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Mutations disrupting the nuclear localization of the RNA-binding protein FUS characterize a subset of amyotrophic lateral sclerosis patients (ALS-FUS). FUS regulates nuclear RNAs, but its role at the synapse is poorly understood. Using super-resolution imaging we determined that the localization of FUS within synapses occurs predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosomes, we identified synaptic FUS RNA targets, encoding proteins associated with synapse organization and plasticity. Significant increase of synaptic FUS during early disease in a mouse model of ALS was accompanied by alterations in density and size of GABAergic synapses. mRNAs abnormally accumulated at the synapses of 6-month-old ALS-FUS mice were enriched for FUS targets and correlated with those depicting increased short-term mRNA stability via binding primarily on multiple exonic sites. Our study indicates that synaptic FUS accumulation in early disease leads to synaptic impairment, potentially representing an initial trigger of neurodegeneration. Mutations in the RNA-binding protein FUS contribute to ALS. Here the authors use CLIP-seq on synaptoneurosomes to identify proteins associated with synapse organization and plasticity that are differentially regulated in a knock-in ALS mouse model.

In Les Furtifs, Alain Damasio imagines a near future where cities are reduced to privatized, hyperconnected spaces dominated by the sense of sight. Creatures born of sound, haunting the blind spots of human vision, the furtifs offer a different relationship with the living. ey embrace human movements, communicate through their words, and imbue them with ambiguity, like a rhythmic power that acts within language. In this article, I would like to discuss the poetics of rhythm at work in Damasio’s novel and to what extent this poetics can be thought of as an ecopoetics, that is, an art of renewing our way of perceiving non human nature through work on language.

En Les Furtifs, Alain Damasio imagina un futuro cercano donde las ciudades se reducen a espacios privatizados, hiperconectados y dominados por el sentido de la vista. Criaturas nacidas del sonido, que rondan los puntos ciegos de la visión humana, los furtivos ofrecen otra relación con los vivos. Abrazan los movimientos de los humanos, se comunican a través de sus palabras, los cargan de ambigüedades, como una potencia rítmica que actúa en el lenguaje. En este artículo mi objetivo es de discutir qué poética del ritmo está presente en Damasio y hasta qué punto esta poética puede ser pensada como una ecopoética, es decir, un arte de renovar nuestra manera de percibir la naturaleza no humana a través del trabajo sobre el lenguaje.

Hexanucleotide G₄C₂ repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Dipeptide repeat proteins (DPRs) generated by translation of repeat-containing RNAs show toxic effects in vivo as well as in vitro and are key targets for therapeutic intervention. We generated human antibodies that bind DPRs with high affinity and specificity. Anti-GA antibodies engaged extra- and intra-cellular poly-GA and reduced aggregate formation in a poly-GA overexpressing human cell line. However, antibody treatment in human neuronal cultures synthesizing exogenous poly-GA resulted in the formation of large extracellular immune complexes and did not affect accumulation of intracellular poly-GA aggregates. Treatment with antibodies was also shown to directly alter the morphological and biochemical properties of poly-GA and to shift poly-GA/antibody complexes to more rapidly sedimenting ones. These alterations were not observed with poly-GP and have important implications for accurate measurement of poly-GA levels including the need to evaluate all centrifugation fractions and disrupt the interaction between treatment antibodies and poly-GA by denaturation. Targeting poly-GA and poly-GP in two mouse models expressing G₄C₂ repeats by systemic antibody delivery for up to 16 mo was well-tolerated and led to measurable brain penetration of antibodies. Long-term treatment with anti-GA antibodies produced improvement in an open-field movement test in aged C9orf72 450 mice. However, chronic administration of anti-GA antibodies in AAV-(G₄C₂)149 mice was associated with increased levels of poly-GA detected by immunoassay and did not significantly reduce poly-GA aggregates or alleviate disease progression in this model.

Cet article discute la manière singulière dont Wajdi Mouawad, dans Anima, imagine une intrigue entièrement prise en charge par le point de vue d’animaux-témoins. À chaque chapitre du roman, le lecteur se trouve en effet introduit dans un monde animal - parent proche des Umwelten du biologiste Uexküll - à partir duquel les faits de l’intrigue lui sont communiqués. Dans cet essai, nous suggérons que l’agentivité attribuée aux animaux permet de compliquer les rôles de sujet et d’objet qui sont d’ordinaires attribués aux acteurs humains et non-humains.

Sirt3 is a mitochondrial NAD + -dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout ( LDLR − / − ) and LDLR / Sirt3 double-knockout ( Sirt3 − / − LDLR − / − ) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3 -deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic core diameter). Likewise, plaque macrophage and T cell infiltration as well as endothelial activation remained unaltered. Electron microscopy of aortic walls revealed no difference in mitochondrial microarchitecture between both groups. Interestingly, loss of Sirt3 was associated with accelerated weight gain and an impaired capacity to cope with rapid changes in nutrient supply as assessed by indirect calorimetry. Serum lipid levels and glucose tolerance were unaffected by Sirt3 deletion in LDLR − / − mice. Sirt3 deficiency does not affect atherosclerosis in LDLR − / − mice. However, Sirt3 controls systemic levels of oxidative stress, limits expedited weight gain, and allows rapid metabolic adaptation. Thus, Sirt3 may contribute to postponing cardiovascular risk factor development.

In a letter Charles Pierre Baudelaire sent from Brussels to Charles Asselineau, conveying his skepticism about his doctor's ability to identify the cause of his illness, the poet expressed himself in a language strangely reminiscent of his final poetic works: \"And the doctor pronounced the big word: Hysteria. The poet attempts to make his readers aware of a yawning gap in their collective memory with regards to the animal's daily work alongside poor men and street performers. In this essay, Weber discusses how this poetic tribute defines its own style by recombining and revising other styles of representation.