3,839 research outputs found
Claudio D’Amato Guerrieri e la “scuola barese” di architettura. Storia e prospettiva dal basso
No full textIl saggio scritto da Giuseppe Fallacara mira alla costruzione di una possibile e auspicabile più ampia storia sulla nascita ed evoluzione della “scuola barese” di architettura, ove per “baresità” si intende la specificità dell’identità degli studi della Facoltà di Architettura di Bari, voluta dal suo fondatore Claudio D’Amato Guerrieri, giunta al suo trentesimo anniversario: dal 1990 ad oggi. Per “dal basso” si deve intendere una molteplicità di significati, primo fra tutti il fatto che questa storia è scritta da un allievo di D’Amato, e quindi allievo della “scuola barese”, che dal basso della gerarchia accademica, ovvero da studente, ha vissuto tutti i trent’anni dai banchi di scuola sino all’ottenimento della cattedra da Professore Ordinario di Composizione Architettonica, avvenuta il primo di aprile del 2020. Dal basso indica anche geograficamente il luogo della pietra, di quella materia prima amata e studiata, costantemente e intensamente, al fianco di D’Amato. Pietra o cultura della pietra che hanno caratterizzato fortemente l’indirizzo formativo della “scuola barese” a cui tutto metaforicamente poteva riferirsi: dalla sua “durezza” alla “naturale” dolcezza dei suoi frutti. Dal basso indica infine, in termini nazionali, il nostro Sud, luogo della nostra facoltà, terra della koinè culturale mediterranea, dai caratteri e storia appartenenti a quel posto della Terra dove e identificabile la culla della sua cultura
Annuario accademico per l'anno 1893-94
No full textPaginazione dell'edizione cartacea: 480 p ; 26 cm. - Riproduzione digitale dell'edizione: Torino : Stamperia Reale, 1894. - Annuario dell'Università degli Studi di Torino (1893-94). - (Contiene il discorso inaugurale "La ricerca delle leggi fisiche" del Prof. Giuseppe Basso. - Cenni biografici su Giusto Emanuele Garelli della Morea, Giuseppe Bruno, Giacinto Pacchiotti e Giacomo Moleschott
Dottrine politiche, concetti, comunità di discorso. In dialogo con Merio Scattola
No full textIl quaderno raccoglie la rielaborazione dei materiali di due convegni dedicati a
tematiche della ricerca di Merio Scattola, svoltisi presso l’Università degli Studi di
Padova con il supporto del Dipartimento di Scienze Storiche, Geografiche e
dell’Antichità, del Dipartimento di Studi Linguistici e Letterari e il patrocinio della
Scuola Galileiana di Studi Superiori. Vengono qui pubblicati i contributi di José
Luis Villacañas, Giuseppe Duso, Michele Basso, Adone Brandalise, Angela De Benedictis, Maurizio Merlo, Luise Schorn-Schütte, Paolo Slongo, Alfredo Viggiano.
Il quaderno si chiude con un breve ma significativo ricordo di Merio da parte di
Michael Stolleis. Lo scopo è quello di continuare il dialogo con Merio su alcune
questioni interdisciplinari che a lungo sono state oggetto di comune ricerca. La
nota introduttiva a cura di Michele Basso e Mario Piccinini enuncia le ragioni di
fondo della scelta dei temi e dell’approccio prescelto. Si ringraziano per la collaborazione Marco Geuna, Claudia Passarella, Paolo Scotton e Antonio Staud
Myocarditis. Reply
No full textTo the Editor: In the review article on myocarditis by Basso (Oct. 20 issue),(1) the author recommends invasive coronary angiography for diagnostic workup in patients with suspected myocarditis in order to rule out underlying coronary artery disease (CAD).(1) Strong evidence suggests that noninvasive coronary computed tomographic angiography (CCTA) has similar diagnostic accuracy and is associated with a lower incidence of adverse events than invasive coronary angiography in patients with chronic coronary syndrome.(2) In fact, recent guidelines on the management of chest pain(3) and prevention of sudden cardiac death(4) recommend CCTA as a class I indication, which should be preferred over . .
Experience of 3711 stapled haemorrhoidectomy operations.
No full textExperience of 3711 stapled haemorrhoidectomy operations (Br J Surg 2006; 93: 226–230) Sir This is the largest series from a single centre. We note that the authors have performed 3,711 operations in 56 months, which is 66 operations/month or 17/week, uninterruptedly for nearly 5 years. They have employed the technique in a number of patients with not otherwise specified ‘bleeding’ (80·7 per cent), and for ‘haemorrhoid thrombosis’ (3·9 per cent). Surgery is in general indicated only for symptomatic thirddegree haemorrhoids not responding to rubber band ligation, and for prolapsed piles1,2. As a consequence, fewer than 10 per cent of patients referred for specialist treatment need haemorrhoidectomy3. L. Basso, G. Cavallaro and A. Polistena Department of Surgery ‘‘Pietro Valdoni’’, University of Rome ‘‘La Sapienza’’ Medical School, Policlinico ‘‘Umberto I’’, viale del Policlinico, Rome 00161, Ital
Zebrafish model of MLL leukemogenesis; implication for fish favorable model of MLL-related leukemia development
No full textDuring these years of experimental work, my research has been addressed to the investigation of the mixed lineage leukemia (MLL) gene functions in acute leukemias, and in particular, to explore the viability of the zebrafish (Danio rerio) as a model to use for understand the role of human MLL in normal and malignant hematopoiesis.
The MLL gene at human chromosome band 11q23 is an important oncogene that is frequently disrupted by chromosomal translocations with more than 50 partner genes in a variety of high-risk acute leukemias of either myeloid or lymphoid derivation, hence the name MLL. These rearrangements are present at significantly high incidence in infants and in the majority of patients with therapy-related leukemia induced by inhibitors of topoisomerase II.
MLL is a large multi-domain protein that has a global role in the regulation of transcription. In particular MLL is required for normal hematopoiesis and implicated in the maintenance of Hox genes expression.
In this PhD thesis the research aim to study three different aspects of MLL oncogene in acute leukemia. 1. The observation that MLL rearrangements and disease itself may initiate within an undifferentiated hematopoietic stem cell. 2. The assessment of MLL genomic breakpoints distribution within the breakpoint cluster region (bcr) in particular in secondary leukemias samples. 3. The versatile biology and genetic flexibility of zebrafish organism as a vertebrate model for studying human hematopoiesis.
1. The investigation of the cell origin of MLL translocations, was studied with a case of a patient diagnosed with pre-pre-B ALL/t (4;11) leukemia, which during the treatment and after matched bone marrow transplantation (BMT), underwent two consecutive switches from lymphoid to myeloid lineage and vice versa. The high expression of HOXA9 and FLT3 genes remaining genotypically stable in leukemia throughout phenotypic switches, suggests that this leukemia may have originated as a common B/myeloid progenitors. This part of the work has been performed by morphology and flow cytometry analyses combined with the microarray analysis, in order to evaluate gene expression during different phases of disease.
2. The work about the localization of MLL genomic breakpoint junction indicates that translocations in treatment related leukemias occur mainly near precise or precise interchromosomal DNA recombination at the sequence level, and confirms a translocation breakpoint hotspot at 3' region in the bcr intron 8. This part of work has been performed by panhandle PCR analysis, a technique that allows the amplification of the MLL genomic breakpoint junction from a stem-loop template using primers all from MLL. The panhandle PCR also identified a breakpoint junction of the uncovered ARMC3 from band 10p12 and MLL intron 9 in a case of treatment-related myeloid leukemia. ARMC3 protein contains Arm repeats similar to catenin proteins (eg. b-catenin), plakophilins and the tumor suppressor APC. ARMC3 is the first gene of this type disrupted by MLL translocation.
3. The overall high-grade conservation of the molecular pathways governing hematopoiesis between mammals and zebrafish, as well as the identification of several well conserved zebrafish transcription factors mammalian orthologs, permitted the identification and characterization of a 12657 bp cDNA sequence which represents a candidate zebrafish orthologue of the human MLL gene. The major advantages of this system include robust experimental techniques in both genetics and embryology, which have been utilized to model many aspects of human development and diseases. This part of the work has been performed by bioinformatics and classical molecular analyses. After sequencing, the zebrafish mll nucleotide sequence, exon-intron structure, amino acid sequence, and conserved domains were analyzed via the zebrafish databases. The temporal pattern of mll mRNA expression was examined using quantitative RT-PCR analysis and whole-mount in situ hybridization analysis. These findings indicate that there is a single mll gene with highly conserved functional similarity to human MLL. The temporal pattern of expression, including maternal supply of transcripts to the embryo, indicates that mll is important from early embryogenesis through the entire lifespan of the fish. The high evolutionary conservation of critical domains creates the starting point to use zebrafish for studying MLL in hematopoiesis and leukemia
MLL partner genes drive distinct gene expression profiles and genomic alterations in pediatric acute myeloid leukemia: an AIEOP study
No full textICER expression inhibits leukemia phenotype and controls tumor progression.
No full textThe inducible cyclic AMP (cAMP) early repressor (ICER) and cAMP response element-binding protein (CREB) are transcriptional regulators of the cAMP-mediated signaling pathway. CREB has been demonstrated to be upregulated in the majority of childhood leukemias contributing to disease progression, whereas ICER, its endogenous repressor, was found to be downregulated. Our research focus has been the function of restored ICER expression. ICER exogenously expressed in cell lines decreases CREB protein level and induces a lowered clonogenic potential in vitro. It decreases the ability of HL60 to invade the extramedullary sites and to promote bone marrow angiogenesis in nonobese diabetic-severe combined immunodeficient mice, demonstrating its potential effects on tumor progression. ICER represses the majority of 96 target genes upregulated by CREB. It binds CRE promoters and controls gene expression restoring the normal regulation of major cellular pathways. ICER is subjected to degradation through a constitutively active form of the extracellular signal-regulated protein kinase, which drives it to the proteasome. We propose that ICER is downregulated in HL60 to preserve CREB overexpression, which disrupts normal myelopoiesis and promotes blast proliferation. These findings define the function of ICER as a tumor suppressor in leukemia. Unbalanced CREB/ICER expression needs to be considered a pathogenetic feature in leukemogenesis. The molecular characterization of this pathway could be useful for novel therapeutic strategies
MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation.
No full textMicroRNA-34b down-regulation in acute myeloid leukemia was previously shown to induce CREB overexpression, thereby causing leukemia proliferation in vitro and in vivo. The role of microRNA-34b and CREB in patients with myeloid malignancies has never been evaluated. We examined microRNA-34b expression and the methylation status of its promoter in cells from patients diagnosed with myeloid malignancies. We used gene expression profiling to identify signatures of myeloid transformation. We established that microRNA-34b has suppressor ability and that CREB has oncogenic potential in primary bone marrow cell cultures and in vivo. MicroRNA-34b was found to be up-regulated in pediatric patients with juvenile myelomonocytic leukemia (n=17) and myelodysplastic syndromes (n=28), but was down-regulated in acute myeloid leukemia patients at diagnosis (n=112). Our results showed that hypermethylation of the microRNA-34b promoter occurred in 66% of cases of acute myeloid leukemia explaining the low microRNA-34b levels and CREB overexpression, whereas preleukemic myelodysplastic syndromes and juvenile myelomonocytic leukemia were not associated with hypermethylation or CREB overexpression. In paired samples taken from the same patients when they had myelodysplastic syndrome and again during the subsequent acute myeloid leukemia, we confirmed microRNA-34b promoter hypermethylation at leukemia onset, with 103 CREB target genes differentially expressed between the two disease stages. This subset of CREB targets was confirmed to associate with high-risk myelodysplastic syndromes in a separate cohort of patients (n=20). Seventy-eight of these 103 CREB targets were also differentially expressed between healthy samples (n=11) and de novo acute myeloid leukemia (n=72). Further, low microRNA-34b and high CREB expression levels induced aberrant myelopoiesis through CREB-dependent pathways in vitro and in vivo. In conclusion, we suggest that microRNA-34b controls CREB expression and contributes to myeloid transformation from both healthy bone marrow and myelodysplastic syndromes. We identified a subset of CREB target genes that represents a novel transcriptional network that may control myeloid transformation
ICER Evokes Dusp1-p38 Pathway Enhancing Chemotherapy Sensitivity in Myeloid Leukemia
No full textPurpose: The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is found downregulated in acute myeloid leukemia (AML), failing to control cAMP response element binding protein (CREB) transcriptional activity, recently demonstrated to mediate AML progression. We aimed to characterize ICER's role in drug sensitivity by treating myeloid cell lines and primary AML with chemotherapics.
Experimental design: The effects on CREB target genes induced by ICER restoration and drug treatment were studied by quantitative real-time PCR (qRT-PCR) and western blot. Cell cycle and apoptosis analysis were performed. Possible ICER-evoked pathways were investigated in vitro. The mechanism involved in enhanced drug sensitivity was described in primary AML cultures by silencing ICER main target genes.
Results: AML cell lines reduced cell growth and enhanced apoptotic behavior after chemotherapy treatment if ICER was expressed. A significantly lowered expression of CREB target genes involved in cell cycle control (CyA1, B1, D1), and in the mitogen-activated protein kinase signaling pathway (ERK, AKT, DUSP1/4), was found after Etoposide treatment. The dual-specificity phosphatases DUSP1 and DUSP4, directly repressed by ICER, activated the p38 pathway, which triggered enhanced caspase-dependent apoptosis. The silencing of DUSP1/4 in HL60 confirmed the same enhanced drug sensitivity induced by ICER. Primary AML cultures, silenced for DUSP1 as well as restored of ICER expression, showed DUSP1 downregulation and p38 activation.
Conclusion: ICER mediates chemotherapy anticancer activity through DUSP1-p38 pathway activation and drives the cell program from survival to apoptosis. ICER restoration or DUSP1 inhibition might be possible strategies to sensitize AML cancer cells to conventional chemotherapy and to inhibit tumor growth. Clin Cancer Res; 17(4); 742-52. (C) 2011 AACR
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