13 research outputs found
Neo-Sumerian Administrative Texts from Umma Kept in the British Museum, Part Five (NATU V)
The present is the fifth volume of the sub-series NATU. In this volume 103 Ur III texts with different contents ranging in time from Šulgi 25 to Ibbi-Suen 2 and a mu-iti text from the former Sargonic period are edited
The Control of Copper and Bronze Manufacts in Umma During the Ur iii Period
The article offers an analysis of the Sumerian administrative documentation from Umma (Djokha) in which the coopersmith are involved. A hypothesis on their role and relationship with the Central Office is put forward
Emoglobinopatie e flussi migratori in Umbria, una regione non endemica
Le emoglobinopatie rappresentano un gruppo eterogeneo di disordini ereditari dell’emoglobina. L’Umbria è una regione considerata storicamente non endemica per tali patologie, tuttavia negli ultimi anni a causa dei flussi migratori la casistica di pazienti affetti seguiti presso il nostro Centro è in continua crescita. Dal 1988 al 2015 sono stati identificati 262 pazienti con alterazioni dei geni alfa o beta globinici (188 beta e 74 alfa), di cui 45 soggetti malati omozigoti o eterozigoti composti per le alterazioni a carico del gene beta globinico e 143 portatori, mentre 40 pazienti con alfa-2 talassemia, 27 con alfa-1 talassemia e 7 con triplicazione del gene alfa. 60% beta-talassemia, 85% drepanocitosi, 40% microdrepanocitosi e l’85% degli eterozigoti composti per varianti beta emoglobiniche sono stati diagnosticati negli ultimi tre anni. Inoltre, la maggior parte degli pazienti beta omozigoti o eterozigoti composti (84,5%) provenivano da paesi stranieri, mentre solo il 15,5% sono di origine italiana (Gorello et al, Hemoglobin). Tale fenomeno non si è arrestato infatti dal 2016 al 2018 sono stati identificati 152 pazienti (range età: 10 giorni-75 anni; rapporto M/F:76/76) aventi mutazioni a carico geni globinici. 104 pazienti con alterazioni a carico del gene beta globinico (2 talassemie, 6 drepanocitosi, 1 microdrepanocitosi, 1 HbE/HbE, 1 HbS/HbC, 93 portatori di varianti quantitative o qualitative); di cui 58 stranieri e 46 Italiani (36 Africani, 5 Americani, 4 Asiatici e 59 Europei). Mentre 48 pazienti con alterazioni a carico dei geni alfa globinici (10 alfa-1 talassemia, 29 alfa-2 talassemia, 2 malattia da HbH, 7 triplo alfa); di cui 30 stranieri e 18 Italiani (12 Africani, 6 Asiatici, 28 Europei e 2 i dati della provenienza non sono disponibili). Complessivamente dal 2012 ad oggi sono stati identificati 307 pazienti (74%) con alterazioni a carico dei geni globinici, di cui il 63% ha un’origine straniera (194 stranieri, 109 Italiani e 4 ND). Tale dato indica il forte incremento di pazienti malati o portatori che necessità quindi di un adeguamento sia in termini diagnostici che di gestione clinica del paziente anche in regioni storicamente non endemiche
Studio molecolare monocentrico di drepanocitosi e varianti falcemiche: valutazione di 6 loci polimorfi in geni regolatori
L’Hb S, variante emoglobinica più diffusa nel mondo, è dovuta a una mutazione a carico del gene beta globinico (HBB:c.20A>T). L’associazione tra alleli codificanti per HbS e alleli caratterizzati da differenti alterazioni possono dare origine a diversi fenotipi. Lo scopo del lavoro è quello di eseguire una caratterizzazione molecolare di pazienti presentanti agli esami di primo livello l’HbS, per effettuare una corretta stratificazione e una stretta correlazione genotipo/fenotipo. Dal 2000 al 2018 sono stati diagnosticati 37 pazienti (range età: 10 gg-60 anni, M/F: 26/10; 25 africani, 6 europei, 3 americani e 3 non disponibili). Lo studio del gene HBB ha permesso di identificare: 20 drepanocitosi, 10 microdrepanocitosi e 7 HbS/HbC. Inoltre sono stati studiati i geni alfa globinici e polimorfismi associati alla variazione di emoglobina fetale, essendo tali fattori possibili modulatori del fenotipo clinico. Nel gruppo dei 20 drepanocitosi (M/F: 17/3; 16 africani, 2 europei e 2 americani) sono stati identificati 5 pazienti con -3.7 in eterozigosi, mentre 1 con -3.7 in omozigosi. Nei 10 microdrepanocitosi (M/F: 7/3; 4 europei, 2 africani, 1 americano e 3 ND) sono stati evidenziati 4 diversi genotipi: HbS/cd39 (C>T), 3 pts; HbS /-29 (A>G), 3 pts; HbS /IVS-I-110 (G>A), 3 pts e HbS /IVS1-6 (T>C), 1 pt. L’analisi dei geni alfa globinici, eseguita in 9/10 pazienti, ha identificato in un paziente (Hb S/ cd 39(C>T)) una triplicazione del gene alfa. Nel gruppo dei 7 HbS/HbC (M/F:3/4; 7 africani) in 2 pazienti è stata riscontrata la mutazione -3.7 in eterozigosi. 33/37 pazienti sono stati analizzati per 5 loci polimorfi: HBG2:g.-158 C>T; BCL11A: rs1427407 G>T e rs10189857 A>G; HBS1L-MYB: rs28384513 A>C e rs9399137 T>C coinvolti nell’espressione della emoglobina fetale; 32/33 pazienti presentavano almeno un polimorfismo e 1/33 (HbS/HbS) è risultato negativo. BCL11A: rs10189857 A>G è il più polimorfo alterato in 19/33 pts (7 microdrepanocitosi, 7 drepanocitosi e 5 eterozigoti composti). HBS1L-MYB: rs9399137 T>C alterato in un paziente (HbS/cd39 (C>T)) risulta essere il meno polimorfo. Lo studio di C/EBPE: rs45496295 C>T è risultato negativo in tutti i pazienti analizzati. Lo studio di nuove alterazioni genetiche, sia nei suddetti locus genici che in altri, e l’incrocio con i dati clinici porterà sempre di più verso una precisa stratificazione dei pazienti, che risulta necessaria sia a fini diagnostici che per la gestione clinica del paziente
Genomic and clinical findings in myeloid neoplasms with PDGFRB rearrangement
Platelet-derived growth factor receptor B (PDGFRB) gene rearrangements define a unique subgroup of myeloid and lymphoid neoplasms frequently associated with eosinophilia and characterized by high sensitivity to tyrosine kinase inhibition. To date, various PDGFRB/5q32 rearrangements, involving at least 40 fusion partners, have been reported. However, information on genomic and clinical features accompanying rearrangements of PDGFRB is still scarce. Here, we characterized a series of 14 cases with a myeloid neoplasm using cytogenetic, single nucleotide polymorphism array, and next-generation sequencing. We identified nine PDGFRB translocation partners, including the KAZN gene at 1p36.21 as a novel partner in a previously undescribed t(1;5)(p36;q33) chromosome change. In all cases, the PDGFRB recombination was the sole cytogenetic abnormality underlying the phenotype. Acquired somatic variants were mainly found in clinically aggressive diseases and involved epigenetic genes (TET2, DNMT3A, ASXL1), transcription factors (RUNX1 and CEBPA), and signaling modulators (HRAS). By using both cytogenetic and nested PCR monitoring to evaluate response to imatinib, we found that, in non-AML cases, a low dosage (100-200 mg) is sufficient to induce and maintain longstanding hematological, cytogenetic, and molecular remissions
Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential for migration.
Glioblastoma (GBM) is the most common and aggressive form of brain tumor, characterized by high migratory behavior and infiltration in brain parenchyma which render classic therapeutic approach ineffective. The migratory behaviour of GBM cells could be conditioned by a number of tissue- and glioma-derived cytokines and growth factors. Although the pro-migratory action of CXCL12 on GBM cells in vitro and in vivo is recognized, the molecular mechanisms involved are not clearly identified. In fact the signaling pathways involved in the pro-migratory action of CXCL12 may differ in individual glioblastoma and integrate with those resulting from abnormal expression and activation of growth factor receptors. In this study we investigated whether some of the receptor tyrosine kinases commonly expressed in GBM cells could cooperate with CXCL12/CXCR4 in their migratory behavior. Our results show a functional cross-talk between CXCR4 and PDGFR which appears to be essential for GBM chemotaxis
Crónicas urbanas e historiografía en la Toscana bajomedieval. Urban chronicles and Historiography in medieval Tuscany
Este trabajo propone una aproximación a la historiografía urbana en Toscana durante la Baja Edad Media. Su cronística se interpreta como resultado de dos fenómenos: la consolidación de Florencia como autoridad política hegemónica en la región y como principal foco cultural del humanismo italiano. Cada epígrafe está dedicado a las historias realizadas sobre una ciudad concreta, interpretándose el contexto de su elaboración, la relación existente entre el autor y los hechos narrados, las características literarias de la obra, su contenido, y las posibilidades y límites que ofrecen para el conocimiento histórico. El catálogo de autores y obras incluye una tipología de las mismas en función de la cronología abordada (periodizaciones acotadas, historias universales y sucesos concretos). Asimismo se precisa los métodos y técnicas de elaboración histórica empleados por los cronistas, y sus esfuerzos humanistas en el tratamiento de las fuentes y por conseguir un estilo literario de inspiración clásica.The aim of this article is to offer a closest view of the urban chronicles made in the Toscana during the transition from the Middle Ages to the Renaissance. The analysis is both historiographic and historic in order to achieve a better comprehension of these Works, taking into account the political evolution of the region and the cultural background that defines it. There for it must be kept in mind that during the Late Medieval Ages Florence gradually grows stronger as the govern authority within the region, as well as the main role in the Italian Humanism.Each one of the sections in this article studies one city. The first one studies the case of Florence, followed by the other cities in the Toscana: Arezzo, Pisa, Pistoia, Prat, San Miniato, Sienna (only city that stays away from the Florentine sovereignty, remaining as a republic) and Volterra. In each case it is studied the historic, institutional and cultural reality surrounding the redaction of the chronicles, the relation between the author and the facts he relates, the literary aspect of the chronicles, in addition its content is summarized, and finally the opportunities and boundaries that the chronicles can offer to the historic knowledge is valued.The chronicles are also classified attending to its characterization. A first differentiation appears when focusing into the way the chronicles deal with the information: some offer just statements that contain the news, with no explanatory recounting, in order to achieve objectivity (Annali Fiorentini, Annali Pisani, Annali Arretonirum); other are detailed essay containing the author’s most intimate feelings (Giovanni de Bonis, Baldasarre Boniaiuti, Antonio Ivani da Sarzana); and there are also Works that join together the explanatory narration with the transcription of public documents from the Comune (Giovanni Villani, Leonardo Bruni, Matteo Palmieri). In order to study this last type of chronicles its been followed the methodology by G. Arnaldi and M. Zabbia about the notary-chronicler, his academic education and notarial work, which leads them to act as attestor and to recount History based in reliable documentation.Another classification can be made according to the chronological period in each chronicle. The Universal Histories go back to the city founding during mythological era and ancient times; they have the most original historical conception, offering chronological frameworks, interpretations and purely humanistic styles (Ricordano Malispini, Baldasarre Bonaiuti, Giovanni Villano, Leonardo Bruni, Niccolò Machiavelli). On the other hand, the cronache cittadine focus in a very precise period and, mostly, contemporary to the writing (Bartolomeo di ser Gorello, Raniero Granchi, Gregorio Dati, Paolo di Tommaso Montauri, Domenico Buoninsegni, Sozomeno da Pistoia, Tommaso Fecini, Francesco Guicciardini). Finally, the ricordanze analyse a very specific and exceptional event (Alamanno Acciaioli, Luigi Guicciardini, Simone Peruzzi, Guccio Benvenuti, Antonio Ivani da Sarzana, Bastiano, Francesco Pezzati, Guasparri Spadari); belonging to this last group there are also some rhymed pieces (Carmen in victoriam Pisanorum, Ricordi di Firenze in 1459, Sacco di Prato de Stefano Guizzalotti). Besides all these chronicle types there are some others in the form of diaries and domestic chronicles (Ugolino di Niccolò Martelli, Matteo Castellani, Filippo Rinuccini).Finally the study focus in the methods and techniques used by the chroniclers in the elaboration of History. They make a record of what they see or know through probative testimonies (oral or written), valuing the document as a source for the elaboration of History. Besides the humanistic way in which the chroniclers handle the sources, they also make an effort to achieve a literary style of classic inspiration
Cross-talk between PDGFRβ and CXCR4.
<p>Time course of CXCL12 (50 nM) induced CXCR4 and PDGFRβ phosphorylation (A) and of PDGFBB (50 ng/ml) induced PDGFRβ and CXCR4 phosphorylation (B). Data are the mean of 5 independent experiments. Western blot analyses of CXCL12- (15 min) and PDGFBB- (15 min) induced PDGFRβ (C) and ERK1/2 (D) phosphorylation in GL15 cells in the presence or in the absence of AG1296 (20 µM, 30 min pre-incubation). E) Western blot analysis of CXCL12- (15 min) and PDGFBB- (15 min) induced CXCR4 phosphorylation in GL15 cells. Insets show representative blots. Results are reported as phosphorylated protein/total protein as percentage of untreated cells. Statistical significance: </p><p>* P<0.05, ** P<0.01, one way Anova or Student’<i>t</i> test followed by Mann-Whitney Rank Sum Test for A and B.</p><p></p
