Multiparametric radiobiological assays show that variation of X-ray energy strongly impacts relative biological effectiveness: comparison between 220 kV and 4 MV

International audienceBased on classic clonogenic assay, it is accepted by the scientific community that, whatever the energy, the relative biological effectiveness of X-rays is equal to 1. However, although X-ray beams are widely used in diagnosis, interventional medicine and radiotherapy, comparisons of their energies are scarce. We therefore assessed in vitro the effects of low- and high-energy X-rays using Human umbilical vein endothelial cells (HUVECs) by performing clonogenic assay, measuring viability/mortality, counting γ-H2AX foci, studying cell proliferation and cellular senescence by flow cytometry and by performing gene analysis on custom arrays. Taken together, excepted for γ-H2AX foci counts, these experiments systematically show more adverse effects of high energy X-rays, while the relative biological effectiveness of photons is around 1, whatever the quality of the X-ray beam. These results strongly suggest that multiparametric analysis should be considered in support of clonogenic assay

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

DNA protection by histone-like protein HU from the hyperthermophilic eubacterium Thermotoga maritima

In mesophilic prokaryotes, the DNA-binding protein HU participates in nucleoid organization as well as in regulation of DNA-dependent processes. Little is known about nucleoid organization in thermophilic eubacteria. We show here that HU from the hyperthermophilic eubacterium Thermotoga maritima HU bends DNA and constrains negative DNA supercoils in the presence of topoisomerase I. However, while binding to a single site occludes ∼35 bp, association of T. maritima HU with DNA of sufficient length to accommodate multiple protomers results in an apparent shorter occluded site size. Such complexes consist of ordered arrays of protomers, as revealed by the periodicity of DNase I cleavage. Association of TmHU with plasmid DNA yields a complex that is remarkably resistant to DNase I-mediated degradation. TmHU is the only member of this protein family capable of occluding a 35 bp nonspecific site in duplex DNA; we propose that this property allows TmHU to form exceedingly stable associations in which DNA flanking the kinks is sandwiched between adjacent proteins. We suggest that T. maritima HU serves an architectural function when associating with a single 35 bp site, but generates a very stable and compact aggregate at higher protein concentrations that organizes and protects the genomic DNA

P2X7 receptor: Death or life?

The P2X7 plasma membrane receptor is an intriguing molecule that is endowed with the ability to kill cells, as well as to activate many responses and even stimulate proliferation. Here, the authors give an overview on the multiplicity and complexity of P2X7-mediated responses, discussing recent information on this receptor. Particular attention has been paid to early and late signs of apoptosis and necrosis linked to activation of the receptor and to the emerging field of P2X7 function in carcinogenesis

Les Mémoires d'outre-tombe ou la restauration du moi par l'écriture mémorialiste

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Raoul Moati. Sartre et le mystère en pleine lumière. Paris, Les Éditions du Cerf, 2019

International audienceDans L’Être et le Néant (1943), après un long réquisitoire contre la psychanalyse, Sartre réhabilite une psychanalyse qui serait celle de la conscience. Sa métaphore oxymorique de « mystère en pleine lumière" désigne l’homme tout en soulignant la dynamique d’élucidation de la réalité psychique visée par la psychanalyse existentielle. Lorsqu’il a suivi les cours d’Alexandre Koyé sur Heidegger, en 1955, Lacan a été marqué par la fonction de vérité comme dévoilement. La psychanalyse existentielle et la psychanalyse lacanienne visent le dévoilement du mystère subjectif. Cependant, la relation analytique, selon Lacan, confronte le sujet au chiffre inconscient de sa destinée mortelle. Pourtant, malgré cette différence radicale et originelle, la pensée sartrienne ne cesse de dialoguer avec celle de Lacan

Chateaubriand, le splendide acteur des Mémoires d’outre-tombe

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L’approche psychanalytique de la littérature dans le cadre d’études académiques ne va pas de soi. Jean-Michel Rabaté, professeur à l’université de Pennsylvanie, éminent spécialiste de James Joyce, de Samuel Beckett et d’André Gide, en démontre tout l’intérêt dans son ouvrage intitulé The Cambridge Introduction to Literature and Psychoanalysis. Il met en perspective le chemin initié par Sigmund Freud et approfondi par Jacques Lacan. Selon Sigmund Freud, les auteurs créatifs ont découvert la vérité à leur insu, ont eu de brillantes intuitions que le psychanalyste peut expliciter. Jacques Lacan ne dira pas autre chose : « Les créations poétiques engendrent, plus qu’elles ne les reflètent, les créations psychologiques.

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Lucile, la vénusté du monde mort

International audienceAccording to Julien Gracq, Memoirs from beyond the Grave could be reduced to the loud squawk made by a peacock in a remote, secluded park in winter time. This striking metaphor underlines how the obsessional writing encircles the traumatic and nodal point of the author. From there we discover the strange relationship Chateaubriand entertained with his sister, Lucile. Chateaubriand was a kind of lonely child in an aristocratic family, so how did he manage, despite the parental couple, to convert this relation with his melancholy sister into the legitimate source of his writing?Selon Julien Gracq, les Mémoires d’outre-tombe de Chateaubriand se résumeraient en un « cri » proféré par le grand paon, depuis un parc isolé et hyémal. Cette métaphore saisissante a le mérite, en particulier, de souligner que l’écriture obsessionnelle de ce texte cerne le point nodal et traumatique de l’auteur. Or nous y découvrons la relation singulière de Chateaubriand à sa sœur Lucile. Comment Chateaubriand, espèce d’enfant unique d’une grande famille aristocratique, a-t-il trouvé son baptême d’écrivain dans le lien à sa sœur mélancolique, pour le légitimer au-delà du couple parental