Scientific Report: International Conference “Medieval Europe in Motion”

Organization The International Conference “Medieval Europe in Motion” took place in Lisbon in April, 18-20 2013. It was organized by Dr. Alicia Miguélez Cavero and Dr. Maria Alessandra Bilotta, being the initiative directly linked to their current postdoctoral research projects. It was also related to other on-going investigations on cultural and artistic circulation during the Middle Ages carried out by the Research Group “Medieval Texts and Images”, coordinated by Prof. Maria Adelaide Miran..

L’enluminure du Midi de la France dans le contexte des circulations culturelles méditerranéennes : un autre manuscrit juridique retrouvé enluminé à Avignon par l’atelier du Liber visionis Ezechielis (Arras, BM, ms. 499 [593]).

Le thème de cet article est l'étude d'un manuscrit juridique enluminé, conservé actuellement dans la Bibliothèque Municipale d’Arras (ms. 499 [593]) : nous avons pu démontrer que ce précieux manuscrit a été illustré et décoré dans le Midi de la France, très probablement à Avignon, dans la première moitié du XIVe siècle par l'atelier dit du Liber de visionis Ezechielis Rotis. Arras,BibliothèqueMunicipale,Décrétales,ms.499[593],f.1rLa découverte de ce manuscrit enrichit le corpus des manuscrit..

la riscoperta di un frammento giuridico miniato bolognese conservato nella Biblioteca Pública di Évora fra storia, storia dell’arte e archeologia del libro

SFRH/BPD/74298/201The systematic study of illuminated juridical manuscripts held in the libraries of Portugal, conducted in the context of a post-doctoral research project funded by the Portuguese Fundação para a Ciência e a Tecnologia (FCT), was the occasion for new analyses and an in-depth study of an interesting set of illuminated juridical fragments in the collection of the Biblioteca Pública of Évora. Among these disiecta membra codi- cum, a fragment belonging to the group called Pergaminhos fragmentados and marked “doc. 97 Pasta 1” – the subject of this paper–provides some useful considerations to help clarify the framework of cultural ties that linked Portugal to the Italian Peninsula in the Middle Ages, and additionally shed light on the dynamics and methods of artistic, cultural and juridical exchange that linked these two regions at this time.publishersversionpublishe

Scientific Report: International Conference “Medieval Europe in Motion”

Organization The International Conference “Medieval Europe in Motion” took place in Lisbon in April, 18-20 2013. It was organized by Dr. Alicia Miguélez Cavero and Dr. Maria Alessandra Bilotta, being the initiative directly linked to their current postdoctoral research projects. It was also related to other on-going investigations on cultural and artistic circulation during the Middle Ages carried out by the Research Group “Medieval Texts and Images”, coordinated by Prof. Maria Adelaide Miran..

Inhibition of bromodomain and extra-terminal (BET) proteins increases NKG2D ligand MICA expression and sensitivity to NK cell-mediated cytotoxicity in multiple myeloma cells. role of cMYC-IRF4-miR-125b interplay

Background: Anticancer immune responses may contribute to the control of tumors after conventional chemotherapy and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of Natural Killer (NK) cells in immune responses toward Multiple Myeloma (MM) and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer. The epigenetic readers of acetylated histones Bromodomain and Extra-Terminal (BET) proteins are critical regulators of gene expression. In cancer, they can upregulate transcription of key oncogenes such as cMYC, IRF4, BCL-2 and others. In addition, the activity of these proteins can regulate the expression of osteoclastogenic cytokines during cancer progression. Here, we investigated the effect of BET-bromodomain proteins inhibition, on the expression of Natural Killer (NK) cell-activating ligands in Multiple Myeloma (MM) cells. Methods: Five MM cell lines [SKO-007(J3), U266, RPMI-8226, ARP-1, JJN3] and CD138+ MM cells isolated from MM patients were used to investigate the activity of BET bromodomain inhibitors (BETi) (JQ1 and I-BET-151) and of the selective BRD4-degrader PROTAC (Proteolysis Targeting Chimera) (ARV-825), on the expression and function of several NK cell activating ligands (NKG2DLs and DNAM-1Ls), using Flow Cytometry, Real-Time PCR, transient transfections and degranulation assays. Results: Our results indicate that inhibition of BET proteins via small molecule inhibitors or their degradation via a hetero-bifunctional Proteolysis Targeting Chimera (PROTAC) probe can enhance the expression of MICA, a ligand of the NKG2D receptor, in human MM cell lines and primary malignant plasma cells, rendering myeloma cells more efficient to activate NK cell degranulation. Noteworthy, similar results were obtained using selective CBP/EP300 bromodomain inhibition. Mechanistically, we found that BETi-mediated inhibition of cMYC correlates with the upregulation of miR-125b-5p and the downregulation of the cMYC/miR-125b-5p target gene IRF4, a transcriptional repressor of MICA. Conclusions: These findings provide new insights on the immuno-mediated antitumor activities of BETi and further elucidate the molecular mechanisms that regulate NK cell-activating ligand expression in MM

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SFRH/BPD/74298/2010 SFRH/BD/115939/2016publishersversionpublishe

Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level

Background It has been demonstrated that Myeloid Derived Suppressor Cells (MDSC) are expanded in HIV-1 infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study we evaluated the frequency of MDSC in patients during primary HIV infection, and factors involved in MDSC control. Methods Patients with primary (PHI) and chronic (CHI) HIV infection were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology. Results We found that granulocytic MDSC (Gr-MDSC) frequency was higher in PHI compared to healthy donors, but lower than CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated to HIV viral load and CD4 T cell count. Interestingly, in PHI Gr-MDSC frequency was inversely correlated with plasmatic level of TRAIL, while a direct correlation was observed in CHI. Further, lower level of GMCSF was observed in PHI compared with CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL induced apoptosis of Gr-MDSC from PHI, can effect that can be abrogated by GM-CSF. Conclusion We found that Gr-MDSC are expanded early during primary HIV infection and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection, and open new perspectives for immune-based strategies

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Images dans les marges des manuscrits toulousains de la première moitié du XIVe siècle: un monde imaginé entre invention et réalité

L’analyse de la décoration marginale des manuscrits produits dans la région toulousaine aux XIIIe et XIVe siècles atteste le développement sur les bords de la Garonne à l’aube du XIVe siècle, de pratiques très intéressantes du point de vue historique et artistique. Dans le dispositif décoratif de ces manuscrits existent en effet quelques singularités qui méritent d’être relevées et qui témoignent de beaucoup d’imagination. Surtout elles apparaissent comme une véritable marque de fabrique des enlumineurs de cette région. Tout en subissant l’influence parisienne, les enlumineurs qui travaillent dans la capitale méridionale ont su maintenir leur originalité. Quelques influences du style linéaire de l’Île-de-France sont prépondérantes à Toulouse et dans le Languedoc comme dans tout l’ensemble du Sud-Est de la France. Cependant l’interprétation que les miniaturistes méridionaux donnent du style septentrional, présente des caractères spécifiques qui ne peuvent que difficilement être confondus avec ceux des autres territoires français et européens. Certains peintres circulent considérablement et contribuent ainsi à une rapide diffusion des nouveautés. Loin de se subordonner à Paris, les ateliers d’enluminure du Midi se sont montrés capables des plus hautes réalisations artistiques. C’est dans cette période que Toulouse devient, à juste titre et par de nombreux aspects, une capitale politique et certainement une capitale culturelle qui voit s’associer des cultures figuratives et littéraires diverses. Cette qualification ne tient pas seulement à l’existence d’un studium important, mais aussi à son rôle de creuset où les expériences et les cultures diverses trouvèrent un espace et des occasions de confrontation et de fusion.Bilotta Maria Alessandra. Images dans les marges des manuscrits toulousains de la première moitié du XIVe siècle : un monde imaginé entre invention et réalité. In: Mélanges de l'École française de Rome. Moyen-Age, tome 121, n°2. 2009. pp. 349-359