Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Self-assembly of Fmoc-tetrapeptides based on the RGDS cell adhesion motif

Self-assembly in aqueous solution has been investigated for two Fmoc [Fmoc ¼ N-(fluorenyl)-9-methoxycarbonyl] tetrapeptides comprising the RGDS cell adhesion motif from fibronectin or the scrambled sequence GRDS. The hydrophobic Fmoc unit confers amphiphilicity on the molecules, and introduces aromatic stacking interactions. Circular dichroism and FTIR spectroscopy show that the self-assembly of both peptides at low concentration is dominated by interactions among Fmoc units, although Fmoc-GRDS shows b-sheet features, at lower concentration than Fmoc-RGDS. Fibre X-ray diffraction indicates b-sheet formation by both peptides at sufficiently high concentration. Strong alignment effects are revealed by linear dichroism experiments for Fmoc-GRDS. Cryo-TEM and smallangle X-ray scattering (SAXS) reveal that both samples form fibrils with a diameter of approximately 10 nm. Both Fmoc-tetrapeptides form self-supporting hydrogels at sufficiently high concentration. Dynamic shear rheometry enabled measurements of the moduli for the Fmoc-GRDS hydrogel, however syneresis was observed for the Fmoc-RGDS hydrogel which was significantly less stable to shear. Molecular dynamics computer simulations were carried out considering parallel and antiparallel b-sheet configurations of systems containing 7 and 21 molecules of Fmoc-RGDS or Fmoc-GRDS, the results being analyzed in terms of both intermolecular structural parameters and energy contributions.

Nomi di parentela

Encyclopedia entry on "Kinship expressions and terms"

Modi di dire

Encyclopedia entry for "idioms" and "idiomatic expressions" in Italian

Dare voce agli invisibili: Il teatro di Beppe Rosso

The article – which is co-authored with Irene Zagrebelsky – focuses on the work of the Italian playwright and actor Beppe Rosso, and it is the most detailed critical account on Rosso’s production so far. Based on original material and interviews, it not only analyses Rosso’s widely acclaimed “Trilogy of invisibility” in the light of recent political events in Italy, but it also – in its first two sections – introduces the so called “teatro di narrazione” to Italian scholars in the UK, and in its two last sections opens up new perspectives on the relationship between contemporary theatre, citizenship and political participation.

Sbiancare un etiope. La pelle cangiante di un topos antico

The book is part of a multi-year investigation on the historical construction and representation of ethnic otherness through the use of language, and focuses on the history of the tópos expressed by the proverb Lavare/sbiancare un etiope (‘to wash an Ethiop white’), a tópos which is traceable in different languages across many centuries (and since II c. A.D.), which stays for either ‘to attempt the impossible’ or ‘to do something useless’. The research also tries to shine a light upon the cultural and social contexts in which ‘Ethiopian’ otherness have generated. Its final goal is to find out how the washing-the-Ethiopian tópos (in its verbal and iconographical forms) has become long-lasting, ductile and semantically productive key expression whose heterogeneous use not only document but also produce and fix otherness in time.

Visual ambiguity in the oeuvre of the Gela Painter: a new lekythos from Thessaly

This paper presents a previously unpublished Attic lekythos and discusses visual ambiguity as an intentional drawing style used by a vase painter who conceptualised the many possible relationships between pot and user, object and subject. The Gela Painter endowed this hastily manufactured and decorated lekythos with visual effects that drew the viewer into an inherently ambivalent motif: a mounting Dionysos. This motif, like other Dionysian themes, had a vogue in late Archaic times but did not necessarily invoke chthonic associations. It had the potential to be consumed in diverse contexts, including religious festivals, by a wide range of audiences. Such images were not given to the viewer fully through visual perception but through interpretation.

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD). LRRK2 contains a Ras of complex proteins (ROC) domain that may act as a GTPase to regulate its protein kinase activity. The structure of ROC and the mechanism(s) by which it regulates kinase activity are not known. Here, we report the crystal structure of the LRRK2 ROC domain in complex with GDP-Mg2+ at 2.0-Å resolution. The structure displays a dimeric fold generated by extensive domain-swapping, resulting in a pair of active sites constructed with essential functional groups contributed from both monomers. Two PD-associated pathogenic residues, R1441 and I1371, are located at the interface of two monomers and provide exquisite interactions to stabilize the ROC dimer. The structure demonstrates that loss of stabilizing forces in the ROC dimer is likely related to decreased GTPase activity resulting from mutations at these sites. Our data suggest that the ROC domain may regulate LRRK2 kinase activity as a dimer, possibly via the C-terminal of ROC (COR) domain as a molecular hinge. The structure of the LRRK2 ROC domain also represents a signature from a previously undescribed class of GTPases from complex proteins and results may provide a unique molecular target for therapeutics in PD.

L'intégration littéraire et iconographique du motif de la descente du Christ aux Enfers à l'ouverture du Merlin

Le début du Merlin et sa mise en image témoignent de l’influence paradoxale du matériau biblique et apocryphe sur la littérature arthurienne, dite "profane". A travers les représentations de la descente aux enfers et le récit de l'effort avorté de conception d'un antéchrist, le roman se joue du texte sacré et de la tradition auxquels il emprunte sa matière. Dans le contexte médiéval, cette réécriture correspond moins à une entreprise de désacralisation et de transgression qu’à la libre continuation du mouvement de réflexion et de création suscité par la matière biblique.

Design and self-assembly of a leucine-enkephalin analogue in different nanostructures: application of nanovesicles

An opioid (leucine-enkephalin) conformational analogue forms diverse nanostructures such as vesicles, tubes, and organogels through self-assembly. The nanovesicles encapsulate the natural hydrophobic drug curcumin and allow the controlled release through cation-generated porogens in membrane mimetic solvent.