Il fumetto come nona arte: proposta di traduzione del fumetto per l’infanzia Akissi

Per il mio elaborato finale ho scelto di proporre la traduzione del fumetto per l’infanzia Akissi scritto dall’autrice ivoriana Marguerite Abouet e reso in immagini dal fumettista Mathieu Sapin. Il racconto tratta di una bambina birbante e scalmanata che, insieme ai suoi amici, anima il tranquillo villaggio di Yopougon, in Costa d’Avorio.

Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: a report from the Children's Oncology Group

To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma.

Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia

Matriptase-2 (Tmprss6), a type II transmembrane serine protease, has an essential role in iron homoeostasis as a hepcidin regulator. Recently, patients with TMPRSS6 mutations and suffering from iron-refractory iron deficiency anaemia (IRIDA) have been reported. We describe two new cases of IRIDA, one patient of Swiss origin and the second of Italian origin. The first case results from a large deletion of 1054 nucleotides corresponding to an in frame deletion of 30 amino acid residues in the low-density lipoprotein receptor-1/-2 (LDLR-1/-2) domains and from a missense mutation in CUB1 (S304L). In the second case, a homozygous G-->C mutation in the last nucleotide of exon 15 and which modified the consensus sequence of the 5' splice donor site of intron 15 (AGgt-->ACgt) was identified. Both patients had a high hepcidin level and low serum iron and transferrin saturation compared to age-matched controls. Continuous perfusion of i.v. iron 4 h/d x 5 d in the first case resulted in a significant rise in haemoglobin. These new cases of IRIDA illustrate the importance of LDLR-1/-2 and CUB1 domains in matriptase-2 function as well as the role of matriptase-2 in hepcidin regulation. Furthermore a deletional form of TMPRSS6 (in LDLR-1/-2 domains) resulting in IRIDA is described for the first time. These cases reinforce the belief that patients suffering from IRIDA have no specific geographical or ethnic distribution and are sporadic secondary to different mutations of the matriptase-2 gene.

In vitro rescue of FGA deletion by lentiviral transduction of an afibrinogenemic patient's hepatocytes.

BACKGROUND: Congenital afibrinogenemia is a rare inherited autosomal recessive disorder in which a mutation in one of three genes coding for the fibrinogen polypeptide chains Aα, Bβ and γ results in the absence of a functional coagulation protein. A patient with congenital afibrinogenemia, resulting from an FGA homozygous gene deletion, underwent an orthotopic liver transplant that resulted in complete restoration of normal hemostasis. The patient's explanted liver provided a unique opportunity to further investigate a potential novel treatment modality. OBJECTIVE: To explore a targeted gene therapy approach for patients with congenital afibrinogenemia. METHODS AND RESULTS: At the time of transplant, the patient's FGA-deficient hepatocytes were isolated and transduced with lentiviral vectors encoding the human fibrinogen Aα-chain. FGA-transduced hepatocytes produced fully functional fibrinogen in vitro. CONCLUSIONS: Orthotopic liver transplantation is a possible rescue treatment for failure of on-demand fibrinogen replacement therapy. In addition, we provide evidence that hepatocytes homozygous for a large FGA deletion can be genetically modified to restore Aα-chain protein expression and secrete a functional fibrinogen hexamer.

STUDIES OF THE MOLECULAR MECHANISMS OF CHROMOSOME ABERRATION FORMATION (DNA REPAIR, CROSSLINKS, MITOMYCIN C)

The objective of this research has been to study the molecular basis for chromosome aberration formation. Predicated on a variety of data, Mitomycin C (MMC)-induced DNA damage has been postulated to cause the formation of chromatid breaks (and gaps) by preventing the replication of regions of the genome prior to mitosis. The basic protocol for these experiments involved treating synchronized Hela cells in G(,1)-phase with a 1 (mu)g/ml dose of MMC for one hour. After removing the drug, cells were then allowed to progress to mitosis and were harvested for analysis by selective detachment. Utilizing the alkaline elution assay for DNA damage, evidence was obtained to support the conclusion that Hela cells can progress through S-phase into mitosis with intact DNA-DNA interstrand crosslinks. A higher level of crosslinking was observed in those cells remaining in interphase compared to those able to reach mitosis at the time of analysis. Dual radioisotope labeling experiments revealed that, at this dose, these crosslinks were associated to the same extent with both parental and newly replicated DNA. This finding was shown not to be the result of a two-step crosslink formation mechanism in which crosslink levels increase with time after drug treatment. It was also shown not to be an artefact of the double-labeling protocol. Using neutral CsCl density gradient ultracentrifugation of mitotic cells containing BrdU-labeled newly replicated DNA, control cells exhibited one major peak at a heavy/light density. However, MMC-treated cells had this same major peak at the heavy/light density, in addition to another minor peak at a density characteristic for light/light DNA. This was interpreted as indicating either: (1) that some parental DNA had not been replicated in the MMC treated sample or; (2) that a recombination repair mechanism was operational. To distinguish between these two possibilities, flow cytometric DNA fluorescence (i.e., DNA content) measurements of MMC-treated and control cells were made. These studies revealed that the mitotic cells that had been treated with MMC while in G(,1)-phase displayed a 10-20% lower DNA content than untreated control cells when measured under conditions that neutralize chromosome condensation effects (i.e., hypotonic treatment). These measurements were made under conditions in which the binding of the drug, MMC, was shown not to interfere with the stoichiometry of the ethidium bromide-mithramycin stain. At the chromosome level, differential staining techniques were used in an attempt to visualize unreplicated regions of the genome, but staining indicative of large unreplicated regions was not observed. These results are best explained by a recombinogenic mechanism. A model consistent with these results has been proposed.^

Réflexions, ou sentences et maximes morales, de Monsieur de LaRochefoucault

Pensées diverses verf. von Petrus , Maximes chrétiennes verf. von Marguerite de Rambouillet de LaSablière