Contra et adversus dominum ducem Mediolani. Percorsi, pratiche e protagonisti della diplomazia fiorentina all'alba delle guerre antiviscontee del Quattrocento

Based on a large corpus of archival sources, and on an extensive bibliography, this research sheds a light on several innovative elements regarding the study of political and diplomatic exchanges in Italy during the first Quattrocento. Through the three parts of the thesis, the analysis of the sources (from the point of view not only of the contents, but also a linguistic one) has clarified the meanings of the war between Florence and Venice against Philippe Marie Visconti. The importance of this work remains first and foremost in the chronological range analyzed: the 1420s are almost absent in the historiography on Italian diplomacy during the Renaissance, a vacuum that can certainly be alleged at a documentary polarization (archives sources become richer from the second half of the century). Secondly, the documentary basin included more than 60 archive collections, which gave the research a solid basis for continuing the historical inquiry, as well as the dialogue established between the different sources. As for the results, beyond the strictly event-oriented plan, from the phenomenon point of view, we have been able to identify the political-territorial evolution of the Italian powers during the first part of the century, long before the crucial moment of the 'Lega Italica' 1455), which is usually the starting point of any diplomatic analysis. It has been possible for us, for example, to go back to the source of the links between Eugene IV and the Medici; or to show the reasons and the issues of the rise of Savoy in Italy; or, finally, to highlight, within Italian political life, the evolution of the papal presence, which shifted from neutrality to the management of diplomatic alliances.En s'appuyant sur un corpus de sources d'archives décidément vaste, et sur une ample bibliographie, cette recherche apporte plusieurs éléments novateurs à l'étude des échanges politiques et diplomatiques dans l'Italie du premier Quattrocento. Au fil des trois parties dont cette thèse se compose, l'analyse des sources (du point de vue non seulement des contenus, mais aussi linguistique) a permis quelques éclaircissements sur la guerre entre Florence et Venise contre Philippe Marie Visconti. L'importance de ce travail réside tout d'abord dans la fourchette chronologique prise en compte : les années Vingt du Quattrocento, en effet, sont quasiment absentes dans l'historiographie sur la diplomatie italienne à la Renaissance, un vide qui peut assurément être allégué à une polarisation documentaire conséquente (les sources d'archives se font plus riches à partir de la seconde moitié du siècle). Deuxièmement, le bassin documentaire a compris plus de 60 fonds d'archives, ce qui a donné à la recherche une base solide pour poursuivre l'enquête historique, grâce aussi à l'osmose et au dialogue établis entre les différentes sources. Quant aux résultats, au-delà du plan strictement événementiel, en ce qui concerne les phénomènes et les trajectoires nous avons pu identifier les évolutions politico-territoriales des puissances italiennes durant la première partie du siècle, bien avant, donc, le moment crucial de la 'Lega italica' (1455), qui est d'habitude vue comme le point de départ de toute analyse diplomatique. Il nous a été possible, par exemple, de remonter jusqu'à la source des liens entre Eugène IV et les Médicis ; ou de montrer les raisons et les enjeux de la montée de la Savoie en Italie ; ou, enfin, de mettre en exergue, au sein de la vie politique italienne, l'évolution de la présence pontificale, qui passa de la neutralité à la gestion des alliances diplomatiques

Novel induced mlo mutant alleles in combination with site-directed mutagenesis reveal functionally important domains in the heptahelical barley Mlo protein

<p>Abstract</p> <p>Background</p> <p>Recessively inherited natural and induced mutations in the barley <it>Mlo </it>gene confer durable broad-spectrum resistance against the powdery mildew pathogen, <it>Blumeria graminis </it>f.sp. <it>hordei</it>. <it>Mlo </it>codes for a member of a plant-specific family of polytopic integral membrane proteins with unknown biochemical activity. Resistant barley <it>mlo </it>mutant alleles identify amino acid residues that are critical for Mlo function in the context of powdery mildew susceptibility.</p> <p>Results</p> <p>We molecularly analyzed a novel set of induced barley <it>mlo </it>mutants and used site-directed mutagenesis in combination with transient gene expression to unravel novel amino acid residues of functional significance. We integrate these results with previous findings to map functionally important regions of the heptahelical Mlo protein. Our data reveal the second and third cytoplasmic loop as being particularly sensitive to functional impediment by mutational perturbation, suggesting that these regions are critical for the susceptibility-conferring activity of the Mlo protein. In contrast, only mutations in the second but not the third cytoplasmic loop appear to trigger the Endoplasmic Reticulum-localized quality control machinery that ensures the biogenesis of properly folded membrane proteins.</p> <p>Conclusion</p> <p>Our findings identify functionally important regions of the polytopic barley Mlo protein and reveal the differential sensitivity of individual protein domains to cellular quality control.</p

Molecular diversity, population structure, and linkage disequilibrium in a worldwide collection of tobacco (Nicotiana tabacum L.) germplasm

<p>Abstract</p> <p>Background</p> <p>The goals of our study were to assess the phylogeny and the population structure of tobacco accessions representing a wide range of genetic diversity; identify a subset of accessions as a core collection capturing most of the existing genetic diversity; and estimate, in the tobacco core collection, the extent of linkage disequilibrium (LD) in seven genomic regions using simple sequence repeat (SSR) markers. To this end, a collection of accessions were genotyped with SSR markers. Molecular diversity was evaluated and LD was analyzed across seven regions of the genome.</p> <p>Results</p> <p>A genotyping database for 312 tobacco accessions was profiled with 49 SSR markers. Principal Coordinate Analysis (PCoA) and Bayesian cluster analysis revealed structuring of the tobacco population with regard to commercial classes and six main clades were identified, which correspond to "Oriental", Flue-Cured", "Burley", "Dark", "Primitive", and "Other" classes. Pairwise kinship was calculated between accessions, and an overall low level of co-ancestry was observed. A set of 89 genotypes was identified that captured the whole genetic diversity detected at the 49 loci. LD was evaluated on these genotypes, using 422 SSR markers mapping on seven linkage groups. LD was estimated as squared correlation of allele frequencies (<it>r²</it>). The pattern of intrachromosomal LD revealed that in tobacco LD extended up to distances as great as 75 cM with <it>r²</it>> 0.05 or up to 1 cM with <it>r²</it>> 0.2. The pattern of LD was clearly dependent on the population structure.</p> <p>Conclusions</p> <p>A global population of tobacco is highly structured. Clustering highlights the accessions with the same market class. LD in tobacco extends up to 75 cM and is strongly dependent on the population structure.</p

Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors.

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer