À quelques pas des lignes. Correspondance 1914-1918 Victor Tardieu & Jean Tardieu, Introduction de G. Turolla traduite par M. Galey

Nel dicembre 2014 avevo avuto modo di consultare e catalogare, su richiesta di Alix Tardieu Turolla, l’archivio contenente le lettere scambiate tra il padre Jean (1903-1995), celebre poeta e drammaturgo, e il nonno Victor (1870-1937), pittore formatosi in ambiente accademico ma dotato di notevole talento e raffinatezza. Tale materiale, di indubbio interesse per la comprensione di entrambe le figure artistiche, è tornato nelle mani del nipote del poeta, Giacomo Turolla, che ne ha tratto un’edi..

Charles Baudelaire, L'Ivrogne

Dalla poesia (i cinque componimenti della terza sezione delle Fleurs du Mal e il celebre poème en prose, Enivrez-vous, dello Spleen de Paris), alla prosa (il saggio narrativo Du vin et du hachisch) fino alla meno nota produzione teatrale (L’Ivrogne), la tematica del vino attraversa tutta l’opera di Charles Baudelaire, quale occasione per riflettere sul potenziale creativo e l’infinita aspirazione umana. Se tali presupposti dell’antropologia baudelairiana sono stati già ampiamente trattati dalla critica, attraverso l’analisi dei testi in versi e in prosa, ci pare che l’apporto fornito dal moderno scénario presenti ancora numerosi spunti d’interesse. Come sottolineato da Georges Bataille (La Littérature et le mal), L’Ivrogne, opera sfortunatamente rimasta in fieri, fonde il sentimento empatico e il delirio del limite umano, mettendo in scena “un’estetica dell’impossibile”, condensata nella valenza simbolica del vino e nella fisionomia di un anti-eroe inedito, l’operaio di una segheria.Wine is a recurring theme in Charles Baudelaire’s literary works, in his poetry (e.g. the five poems in the third section of Les Fleurs du Mal, and the famous prose poem Enivrez-vous in Le Spleen de Paris) as well as in his prose (e.g. the narrative essay Du vin et du hachisch), not to mention his lesser-known dramatic text L’Ivrogne. In his works, wine often serves as a pretext to reflect on artistic creation and men’s boundless aspirations. If, on the one hand, these fundamental aspects of Baudelaire’s anthropology have already been treated by scholars, on the other, the modern script still offers several interesting prompts for further research. As George Bataille wrote in La Littérature et le mal, L’Ivrogne, a work that Baudelaire unfortunately never finished, tries to create a blend of empathy and madness, putting on stage «an aesthetic of the impossible», represented by the symbolic value of wine and the creation of an original anti-hero, a sawmill worker

Activation of an endothelial Notch1-Jagged1 circuit induces VCAM1 expression, an effect amplified by interleukin-1β

The Notch1 and Notch4 signaling pathways regulate endothelial cell homeostasis. Inflammatory cytokines induce the expression of endothelial adhesion molecules, including VCAM1, partly by downregulating Notch4 signaling. We investigated the role of endothelial Notch1 in this IL-1β-mediated process. Brief treatment with IL-1β upregulated endothelial VCAM1 and Notch ligand Jagged1. IL-1β decreased Notch1 mRNA levels, but levels of the active Notch1ICD protein remained constant. IL-1β-mediated VCAM1 induction was downregulated in endothelial cells subjected to pretreatment with a pharmacological inhibitor of the γ-secretase, which activates Notch receptors, producing NotchICD. It was also downregulated in cells in which Notch1 and/or Jagged1 were silenced.Conversely, the forced expression of Notch1ICD in naïve endothelial cells upregulated VCAM1 per se and amplified IL-1β-mediated VCAM1 induction. Jagged1 levels increased and Notch4 signaling was downregulated in parallel. Finally, Notch1ICD and Jagged1 expression was upregulated in the endothelium of the liver in a model of chronic liver inflammation.In conclusion, we describe here a cell-autonomous, pro-inflammatory endothelial Notch1-Jagged1 circuit (i) triggering the expression of VCAM1 even in the absence of inflammatory cytokines and (ii) enhancing the effects of IL-1β. Thus, IL-1β regulates Notch1 and Notch4 activity in opposite directions, consistent with a selective targeting of Notch1 in inflamed endothelium

Systematic identification of edited microRNAs in the human brain

Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA–mRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread, others deem the reported events as rare. Utilizing a next-generation sequencing (NGS) approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread

β-arrestin1-mediated acetylation of Gli1 regulates Hedgehog/Gli signaling and modulates self-renewal of SHH medulloblastoma cancer stem cells

Background Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of Sonic hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli signaling controls CSCs features in SHH-MB and that in these tumors miR-326 is down regulated, here we investigated whether there is a functional link between Hh/Gli signaling and miR-326. Methods We evaluated β-arrestin1 (Arrb1) and its intragenic miR-326 levels in CSCs derived from SHH-MB. Subsequently, we modulated the expression of Arrb1 and miR-326 in CSCs in order to gain insight into their biological role. We also analyzed the mechanism by which Arrb1 and miR-326 control Hh/Gli signaling and self-renewal, using luciferase and protein immunoprecipitation assays. Results Low levels of Arrb1 and miR-326 represent a feature of CSCs derived from SHH-MB. We observed that re-expression of Arrb1 and miR-326 inhibits Hh/Gli signaling pathway at multiple levels, which cause impaired proliferation and self-renewal, accompanied by down regulation of Nanog levels. In detail, miR-326 negatively regulates two components of the Hh/Gli pathway the receptor Smoothened (Smo) and the transcription factor Gli2, whereas Arrb1 suppresses the transcriptional activity of Gli1, by potentiating its p300-mediated acetylation. Conclusions Our results identify a new molecular mechanism involving miR-326 and Arrb1 as regulators of SHH-MB CSCs. Specifically, low levels of Arrb1 and miR-326 trigger and maintain Hh/Gli signaling and self-renewal

Feasibility and Acceptability of a Real-Time Telerehabilitation Intervention for Children and Young Adults with Acquired Brain Injury During the COVID-19 Pandemic: An Experience Report

This study examined the feasibility and acceptability of a telerehabilitation intervention during the COVID-19 pandemic in a sample of children and young adults with Acquired Brain Injury (ABI). Thirteen patients and/or their families agreed to participate in the speech and neuropsychological telerehabilitation sessions. The treatment was synchronous, patient centered and aimed at improving specific abilities. Sessions were held twice a week over a 10-week period. Two questionnaires were completed both by parents and therapists to assess feasibility and acceptability. Neither technical issues nor clinical obstacles were found. The quality of the therapeutic relationship played a key role in the intervention. Synchronous telerehabilitation provided several advantages both for patients and therapists. Moreover, the patient centered intervention eased the burden of the caregivers at a time of high stress. The real-time telerehabilitation treatments were deemed suitable for children and young adults with ABI. Further studies are needed to support the use of telerehabilitation as an integral part of their standard care

THE COURSE OF ASTHMA DURING PREGNANCY IN A RECENT, MULTICASE-CONTROL STUDY ON RESPIRATORY HEALTH

Background Over the years it has been widely stated that approximately one third of asthmatic women experience worsening of the disease during pregnancy. However, the literature has not been reviewed systematically and the meta-analytic reviews include old studies. This study aimed to examine whether the prevalence of worsening asthma during pregnancy is still consistent with prior estimate or it has been reduced. Methods A detailed Clinical Questionnaire on respiratory symptoms, medical history, medication, use of services, occupation, social status, home environment and lifestyle was administered to random samples of the Italian population in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Only clinical data belong to 2.606 subjects that completed the clinical stage of the GEIRD study, were used for the present study. Results Out of 1.351 women, 284 self-reported asthma and 92 of them had at least one pregnancy. When we considered the asthma course during pregnancy, we found that 16 women worsened, 31 remained unchanged, 25 improved. Seven women had not the same course in the different pregnancies and 13 did not know. The starting age of ICS use almost overlaps with that of asthma onset in women with worsening asthma during pregnancy (19 years \ub11.4), unlike the other women who started to use ICS much later (30.3 years \ub112). In addition, the worsening of asthma was more frequent in women with an older age of onset of asthma (18 years \ub19 vs 13 years \ub110). Among women who completed the ACT during the clinical interview, the 50% of women who experienced worsening asthma during pregnancy (6/12) had an ACT score below 20. Conclusion Asthma was observed to worsen during pregnancy in a percentage much lower to that generally reported in all the previous studies. There is still room in clinical practice to further reduce worsening of asthma during pregnancy by improving asthma control, with a more structured approach to asthma education and management prepregnanc