Early onset and enhanced growth of autochthonous mammary carcinomas in C3-deficient Her2/neu transgenic mice

Aside from its classical role in fighting infections, complement is an important, although poorly understood, component of the tumor microenvironment. In particular, the tumor growth-regulatory activities of complement remain under debate. To assess the role of the complement system in the progression of autochthonous mammary carcinomas, we have crossed complement component 3 (C3)-deficient (C3(−/−)) BALB/c male mice with BALB/c females expressing the activated rat Her2/neu oncogene (neuT). Although neuT transgenic mice develop spontaneous mammary cancers with 100% penetrance, a significantly shorter tumor latency (i.e., earlier onset of the first palpable tumor), a higher frequency of multiple tumors (multiplicity), and a dramatic increase in the tumor growth rate were found in neuT-C3(−/−) animals. The accelerated tumor onset observed in neuT-C3(−/−) mice was paralleled by an earlier onset of spontaneous lung metastases and by an increase in Her2 expression levels, primarily on the surface of tumor cells. The percentage of immune cells infiltrating neuT carcinomas was similar in C3-deficient and C3-proficient mice, with the exception of a significant increase in the frequency of regulatory T cells in neuT-C3(−/−) tumors. Of particular interest, the enhanced immunosuppression imparted by C3 deficiency clearly influenced the immunogenic phenotype of autochthonous mammary tumors as neuT-C3(−/−) malignant cells transplanted into syngeneic immunocompetent hosts gave rise to lesions with a significantly delayed kinetics and reduced incidence as compared with cells obtained from neuT C3-proficient tumors. Finally, increased blood vessel permeability was evident in neuT-C3(−/−) tumors, although a similar number of tumor vessels was found in neuT and neuT-C3(−/−) lesions. Altogether, these data suggest that complement plays a crucial role in the immunosurveillance and, possibly, the immunoediting of Her2-driven autochthonous mammary tumors

Genetic variability of the grey wolf Canis lupus in the Caucasus in comparison with Europe and the Middle East: distinct or intermediary population?

Despite continuous historical distribution of the grey wolf (Canis lupus) throughout Eurasia, the species displays considerable morphological differentiation that resulted in delimitation of a number of subspecies. However, these morphological discontinuities are not always consistent with patterns of genetic differentiation. Here we assess genetic distinctiveness of grey wolves from the Caucasus (a region at the border between Europe and West Asia) that have been classified as a distinct subspecies C. l. cubanensis. We analysed their genetic variability based on mtDNA control region, microsatellite loci and genome-wide SNP genotypes (obtained for a subset of the samples), and found similar or higher levels of genetic diversity at all these types of loci as compared with other Eurasian populations. Although we found no evidence for a recent genetic bottleneck, genome-wide linkage disequilibrium patterns suggest a long-term demographic decline in the Caucasian population – a trend consistent with other Eurasian populations. Caucasian wolves share mtDNA haplotypes with both Eastern European and West Asian wolves, suggesting past or ongoing gene flow. Microsatellite data also suggest gene flow between the Caucasus and Eastern Europe. We found evidence for moderate admixture between the Caucasian wolves and domestic dogs, at a level comparable with other Eurasian populations. Taken together, our results show that Caucasian wolves are not genetically isolated from other Eurasian populations, share with them the same demographic trends, and are affected by similar conservation problems

Cornelia Rossi Martinetti

Biografia Cornelia Rossi Martinett

D’un siècle à l’autre, l’Europe dans les manuels scolaires en France et en Italie, in L’Europe: une autre nation?

Confronto manuali italiani e francesi sul tema della costruzione europea

Dalla diffidenza alla riconsiderazione: l’atteggiamento della Gran Bretagna verso la “nuova Italia” (1947-1951)

Riflessione sull'atteggiamento e le considerazioni politiche dell'opinione pubblica inglese sull'Italia del secondo dopoguerra. Fonti inglesi original

Marco Minghetti: una prospettiva europea per i notabili bolognesi nella prima met\ue0 del XIX secolo

Il saggio intende ripercorrere il percorso intellettuale e politico che guid\uf2 Marco Minghetti e con lui tutto quel gruppo di liberali moderati che gravitarono attorno alla sua figura. Un pensiero che si voleva pragmatico e non dogmatico, spinto dalla preoccupazione di utilizzare il progetto liberale per modernizzare la societ\ue0, ma conservando sempre uno sguardo attento all\u2019elaborazione di un modello sociale proprio al contesto italiano. Determinate fu il percorso di formazione dello statista bolognese, che un\uec la lettura dei classici del liberalismo inglese ai viaggi nell\u2019Inghilterra della rivoluzione industriale e alla pratica associativa, all\u2019interno della neo-costituita Societ\ue0 Agraria Bolognese. Il saggio si propone di mostrare come ci\uf2 permise l\u2019elaborazione di una via originale al liberalismo, un \u201cliberalismo misto o plurale, capace di far apparire una via originale nella modernizzazione della societ\ue0 italiana

Faire une nation. Les Italiens et l'unité (XIXe-XXe siècle)

International audienc