Mimèsis et catharsis : de la représentation à la dénégation du réel chez Aristote, Artaud et Brecht

La présente étude propose une relecture de trois théoriciens dont les investigations continuent à servir de pierre angulaire à la théâtrologie : celles d'Aristote dont La Poétique, outre le fait qu'elle consacre le théâtre occidental, sert de fondement à l'esthétique dramatique et celles, plus récentes, d'Antonin Artaud et de Bertolt Brecht qui, bien qu'ils aient réfuté radicalement les théories aristoté- liciennes, ne se sont pas moins distingués l'un de l'autre pour donner les deux grandes voies que l'on sait à la réflexion dramaturgique contemporaine. Ces spéculations seront envisagées sous l'éclairage décisif de la mimèsis et de la catharsis qui ne se posent pas chez eux comme des notions distinctes, mais comme l'avers et l'envers d'un même travail sur un réel à chaque fois redéfini, qu'il s'agisse de l'obéissance aristotélicienne à une stricte logique narrative, de l'utopique déculturation artaudienne ou de l'engagement brechtien.The author proposes a review of three major theoreticians whose works are considered to be the corner-stones of theatrical studies : Aristotle, whose Poetics, the first reflexion on Occidental theatre, also serve as the foundation of the aesthetics of drama, and, closer to us, Antonin Artaud and Bertolt Brecht who, although unanimous in rejecting the Aristotelian theory, have quite different views on contemporary theatre. Their definitions are analyzed in the light of mimesis and catharsis, which are not taken here as separate notions, but rather as a mean of grasping the fluctuant outlines of the concept of "reality", be it Aristotle's obedience to a strict narrative structure, Artaud's denial of culture or Brecht's political commitment

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility