La figure de la sorcière dans la littérature du XIXe siècle (Jules Michelet, George Sand, Eliza Orzeszkowa)

The nineteenth century uncovered and analysed the tragic episodes of witch-hunting and ‘witch’ trials common in Renaissance Europe. Fascinating not only to historians, this subject also inspired men of letters who popularized the image of the witch as an old, ugly and evil person, who thus deserved her lot. Jules Michelet’s La sorcière of 1862 takes a very different approach. Simultaneously a literary and historical work, the book proved scandalous as it rehabilitated the figure of the witch, shedding favourable light on her image: it was the witch who was able to save a last spark of humanity in moments of despair; it was she who acted as comforter and healer to the people. In the context of nineteenth-century literature, certain works by female authors that focused on ‘witches,’ stand out. Whilst certain male authors (Michelet included) presented the witch as a figure from the past, who had finally perished in the 17th century, texts such as George Sand’s La petite Fadette (1848) or Eliza Orzeszkowa’s Dziurdziowie (1885), suggest that the end of witch trials did not imply an end to accusations, persecutions, and even executions of ‘witches’ – and, that in terms of culture, witchcraft or sorcery had not disappeared from the societies they knew.

Dsh homolog DVL3 mediates resistance to IGFIR inhibition by regulating IGF-RAS signaling

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.

Le personnage de la femme-artiste chez l'écrivain polonaise Narcyza Żmichowska (1819-1876) : Helusia héritière de Corinne de Mme de Staël et de Consuelo de George Sand

Si les hommes bénéficient d’emblée de mythes (Pygmalion, Orphée) qui légitiment et motivent leur créativité, il faut attendre Corinne (1807) de Mme Staël et Consuelo (1842) de George Sand pour que le mythe de la femme créatrice trouve enfin, dans la littérature européenne, à se concrétiser et à se développer sous la forme de Künstlerromane féminins. Corinne la poétesse et Consuelo la cantatrice sont devenues des exemples littéraires non seulement pour les femmes victoriennes, comme le montre par exemple le livre de Linda Lewis intitulé Germaine de Staël, George Sand and the Victorian Woman Artist, mais également pour les femmes polonaises issues des classes favorisées - qui lisaient d’ailleurs couramment en français. En effet, même si elles ont été officiellement décriées par la critique conservatrice polonaise pour leur « immoralité », George Sand et Mme de Staël ont été lues, bien lues et même beaucoup lues par leurs contemporaines polonaises - comme le témoigne la correspondance de ces dernières, dans laquelle elles ont moins de peine à se livrer. Le thème de la femme artiste déchirée entre la carrière publique et la vie privée, tel qu’il est représenté dans Corinne et dans Consuelo, a en particulier attiré toute leur attention et suscité chez les femmes écrivains le désir d’apporter de nouvelles manières de résoudre ce conflit. Dans cet article, le Künstlerinroman polonais Książka Pamiątek (Livre des souvenirs, 1846) de Narcyza Żmichowska fait l’objet d’une analyse comparative détaillée avec les deux Künstlerinromane français dont par ailleurs il se réclame.