Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease

The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3′-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patient

Evidence of coat color variation sheds new light on ancient canids.

International audienceWe have used a paleogenetics approach to investigate the genetic landscape of coat color variation in ancient Eurasian dog and wolf populations. We amplified DNA fragments of two genes controlling coat color, Mc1r (Melanocortin 1 Receptor) and CBD103 (canine-β-defensin), in respectively 15 and 19 ancient canids (dogs and wolf morphotypes) from 14 different archeological sites, throughout Asia and Europe spanning from ca. 12 000 B.P. (end of Upper Palaeolithic) to ca. 4000 B.P. (Bronze Age). We provide evidence of a new variant (R301C) of the Melanocortin 1 receptor (Mc1r) and highlight the presence of the beta-defensin melanistic mutation (CDB103-K locus) on ancient DNA from dog-and wolf-morphotype specimens. We show that the dominant K(B) allele (CBD103), which causes melanism, and R301C (Mc1r), the variant that may cause light hair color, are present as early as the beginning of the Holocene, over 10 000 years ago. These results underline the genetic diversity of prehistoric dogs. This diversity may have partly stemmed not only from the wolf gene pool captured by domestication but also from mutations very likely linked to the relaxation of natural selection pressure occurring in-line with this process

Entre hystérisation du lien social et répression culturelle

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Le sport à l'épreuve de la psychanalyse

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La musique, un appareil idéologique d’État. L’Occupation nazie en France

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La musique, un appareil idéologique d’État. L’Occupation nazie en France

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La magie de l'univers musical (perspectives herméneutiques sur l'essence de la musique savante occidentale)

L idée de magie musicale renvoie à une interprétation du rôle de la magie dans la vie psychique. L œuvre musicale est un objet intentionnel tel que le conçoit Roman Ingarden, c est-à-dire un objet qui ouvre un horizon infini de sens. À la fois intérieure et extérieure, immanente et transcendante, temporelle et a-temporelle, réelle et idéelle, intelligible et pathétique, la musique est la coïncidence des opposés. La magie musicale intéresse la psychologie clinique et particulièrement la psychanalyse parce qu elle met en scène des scénarios désirants dont la matière essentielle réside dans l intersubjectivité. À cet égard on peut soutenir l idée de la spécificité de la musique du fait de sa magie potentielle. Art de la temporalité qui organise diverses formes temporelles, la musique constitue un chiasme magique : magie du temps, temps de la magie. Tant au niveau de la création que de l interprétation et de la réception, la musique est la voix du pur désir. En devenant musique, l imaginaire s auto-engendre dans le flux du temps où il s immerge.The idea of music magic leads us to an interpretation of the role of magic in psychic life. As conceived by Roman Ingarden, a musical piece is an intentional object, i.e. an object opening an infinite horizon of meaning. At the same time internal and external, immanent and transcendental, temporal and non-temporal, real and ideal, intelligible and pathetic, music is the coincidence of opposites. Music magic is of interest for clinical psychology, and especially for psychoanalysis, because it breathes life to desiring scenarios, whose essential substance resides in inter-subjectivity. In this regard, it is possible to assert the idea of the specificity of music based on its potential magic. An art of temporality that organises several temporal forms, music constitutes a magical chiasma : magic of time, time of magic, as we find in innumerable opera scores. At creative and interpretative level, as in its reception, music is the voice of pure desire. In becoming music, the imaginary generates itself in the midst of the flux of the very time in which it is immersed.NANTERRE-BU PARIS10 (920502102) / SudocSudocFranceF

Écoutes musicales sur le thème de « Variations musicales sur le thème de la joie (et la tristesse) ».

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Argument

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