Parapoxvirus: basi genomiche della patogenesi

Parapoxvirus (PPV) are member of a genus in the family poxviridae which currently encompasses four species: the prototype orf virus (OV), bovine papular stomatitis virus (BPSV), pseudocowpox virus (PCPV) and parapoxvirus of New Zealand red deer (PVNZ). PPVs cause widespread, but localized diseases of small and large ruminants and they can also be transmitted to man. Knowledge of the molecular biology of PPV is still limited as compared to orthopoxviruses, especially vaccinia virus (VACV). The PPV genome displays a high G+C content and relatively small size for poxvirus. Coventional electron microscopy displays PPV virions with ovoid shape and slightly smaller in size than the brickshaped orthopoxviruses. The most striking feature, which readily enables identification of PPV, is a tubule-like structure that surrounds the particle in a spiral fashion. PPV genome organization and content is very similar to that of other poxviruses, the central region contain 88 genes which are present in all poxviruse, in contrast the terminal regions are variable and contain a set of genes unique to the genus PPV. Genes in the near-terminal regions of the genome are frequently not essential for growth in cultured cells encoding factors with important roles in virushost interactions including modulating host immune responses and determining host range. Recently it was suggested that the open reading frames (ORFs) 109 and 110 of the OV genome have a major role in determining species specificity during natural infection in sheep and goats. This hypothesis is based on the analysis of a few number of sequences of different sheep and goats viral isolates. PPV replicate into the cytoplasm of infected cells and produce three structurally different infectious particles: the intracellular mature virions (IMV), intracellular enveloped virions (IEV) and the extracellular enveloped virions (EEV). The vaccinia A33R and A34R hotologue proteins encoded by the ORFS 109 and 110 are expressed in the envelope of the IEV and EEV. The F1L immunodominant protein of orf virus is the major component of the surface tubule structure of the IMV and can post-translationaly insert into membranes via Cterminal, hydrofobic anchor sequence like its orthologue VACV H3L protein. Moreover the F1L protein binds to glycosaminoglycans on the cell surface and has an important role in IMV adsorption to mammalian cells. In this study we investigated the morphogenesis of the PPV through the construction of a mutant virus deleted of the F1L protein. A study of the deleted virus life cycle was conducted in different type of cells and its morphology was observed with electron microscopy. It was demonstared that F1L protein have important role in morphogenesis and infectivity. Moreover it is essential to determine the spiral fashion of the tubule like structure of the virion surface. Some pathogenetic aspects of the PPV infection were studied, in particular the protein implicated in the host range were analysed in detail. An experimental infection with OV and PCPV was conducted in goats and sheep. After infection, the severity of the lesions were comparable in both the animal species. The OV did not result in severe disease neither in sheep nor in goats, suggesting that host factors, rather than virus strain characteristics, may play an important role in the pathogenesis of the Parapoxvirus infections. The PCPV failed to produce any lesion in both sheep and goats, ruling out the possibility of any recombination between PCPV and OV during natural infection in these animal species. The phylogenetic analysis of the ORFs 109 and 110 from several goats and sheep viral isolates showed a clustering based on the antigenic content of the protein that was independent from species and geographic origin.

Una filologia della società. Antonio Gramsci e la scoperta delle scienze sociali nella crisi dell'ordine liberale

Questa tesi di dottorato ha per suo oggetto la ricognizione degli elementi teorici, di linguaggio politico e di influenza concettuale che le scienze sociali tra Ottocento e Novecento hanno avuto nell’opera di Antonio Gramsci. La ricerca si articola in cinque capitoli, ciascuno dei quali intende ricostruire, da una parte, la ricezione gramsciana dei testi classici della sociologia e della scienza politica del suo tempo, dall’altra, far emergere quelle filiazioni concettuali che permettano di valutare la portata dell’influenza delle scienze sociali sugli scritti gramsciani. Il lungo processo di sedimentazione concettuale del lessico delle scienze sociali inizia in Gramsci già negli anni della formazione politica, sullo sfondo di una Torino positivista che esprime le punte più avanzate del “progetto grande borghese” per lo studio scientifico della società e per la sua “organizzazione disciplinata”; di questa tradizione culturale Gramsci incrocia a più riprese il percorso. La sua formazione più propriamente politica si svolge però all’interno del Partito socialista, ancora imbevuto del lessico positivista ed evoluzionista. Questi due grandi filoni culturali costituiscono il brodo di coltura, rifiutato politicamente ma al tempo stesso assunto concettualmente, per quelle suggestioni sociologiche che Gramsci metterà a frutto in modo più organico nei Quaderni. La ricerca e la fissazione di una specifica antropologia politica implicita al discorso gramsciano è il secondo stadio della ricerca, nella direzione di un’articolazione complessiva delle suggestioni sociologiche che i Quaderni assumono come elementi di analisi politica. L’analisi si sposta sulla storia intellettuale della Francia della Terza Repubblica, più precisamente sulla nascita del paradigma sociologico durkheimiano come espressione diretta delle necessità di integrazione sociale. Vengono così messe in risalto alcune assonanze lessicali e concettuali tra il discorso di Durkheim, di Sorel e quello di Gramsci. Con il terzo capitolo si entra più in profondità nella struttura concettuale che caratterizza il laboratorio dei Quaderni. Si ricostruisce la genesi di concetti come «blocco storico», «ideologia» ed «egemonia» per farne risaltare quelle componenti che rimandano direttamente alle funzioni di integrazione di un sistema sociale. La declinazione gramsciana di questo problema prende le forme di un discorso sull’«organicità» che rende più che mai esplicito il suo debito teorico nei confronti dell’orizzonte concettuale delle scienze sociali. Il nucleo di problemi connessi a questa trattazione fa anche emergere l’assunzione di un vero e proprio lessico sociologico, come per i concetti di «conformismo» e «coercizione», comunque molto distante dallo spazio semantico proprio del marxismo contemporaneo a Gramsci. Nel quarto capitolo si affronta un caso paradigmatico per quanto riguarda l’assunzione non solo del lessico e dei concetti delle scienze sociali, ma anche dei temi e delle modalità della ricerca sociale. Il quaderno 22 intitolato Americanismo e fordismo è il termine di paragone rispetto alla realtà che Gramsci si prefigge di indagare. Le consonanze delle analisi gramsciane con quelle weberiane dei saggi su Selezione e adattamento forniscono poi gli spunti necessari per valutare le novità emerse negli Stati Uniti con la razionalizzazione produttiva taylorista, specialmente in quella sua parte che riguarda la pervasività delle tecniche di controllo della vita extra-lavorativa degli operai. L’ultimo capitolo affronta direttamente la questione delle aporie che la ricezione della teoria sociologica di Weber e la scienza politica italiana rappresentata dagli elitisti Mosca, Pareto e Michels, sollevano per la riformulazione dei concetti politici gramsciani. L’orizzonte problematico in cui si inserisce questa ricerca è l’individuazione di una possibile “sociologia del politico” gramsciana che metta a tema quel rapporto, che è sempre stato di difficile composizione, tra marxismo e scienze sociali.

L'infiammazione intestinale nell'animale sperimentale come modello per lo sviluppo di nuovi farmaci: ruolo della via tachichininergica nelle malattie infiammatorie intestinali

Background: Several lines of evidence showed that inflammation is associated with changes in the expression of tachykinins both in human and animal models. Tachykinins, including substance P (SP), are small peptides expressed in the extrinsic primary afferent nerve fibres and enteric neurons of the gut: they exert their action through three distinct receptors, termed NK1, NK2 and NK3. SP modulates intestinal motility and enteric secretion, acting preferentially through the NK1 receptor. SP neural network and NK1 receptor expression are increased in patients with inflammatory bowel disease, and similar changes were observed in experimental models of inflammation. The 2,4 Dinitrobenzene Sulphonic Acid (DNBS) model of colitis is useful to study innate immunity, non-specific inflammation and wound healing; it has been suggested that the transmural inflammation seen in this model resembles that found in Crohn’s disease and can therefore be used to study what cells and mediators are involved in this type of inflammation. Aim: To test the possible protective effect of the NK1 receptor antagonist SSR140333 on: 1) acute model of intestinal inflammation; 2) reactivation of DNBS-induced colitis in rats. Methods: Acute colitis was induced in male SD rats by intrarectal administration of DNBS (15 mg/rat in 50% ethanol). Reactivation of colitis was induced by intrarectal injections of DNBS on day 28 (7.5 mg/rat in 35% ethanol). Animals were sacrificed on day 6 (acute colitis) and 29 (reactivation of colitis). SSR140333 (10 mg/kg) was administered orally starting from the day before the induction of colitis for 7 days (acute colitis) or seven days before the reactivation of colitis. Colonic damage was assessed by means of macroscopic and microscopic scores, myeloperoxidase activity (MPO) and TNF-α tissue levels. Enzyme immunoassay was used to measure colonic substance P levels. Statistical analysis was performed using analysis of variance (one-way or two-way, as appropriate) with the Bonferroni’s correction for multiple comparisons. Results: DNBS administration impaired body weight gain and markedly increased all inflammatory parameters (p<0.01). Treatment with SSR140333 10 mg/kg significantly counteracted the impairment in body weight gain, decreased macroscopic and histological scores and reduced colonic myeloperoxidase activity (p<0.01). Drug treatment counteracted TNF-α tissue levels and colonic SP concentrations (acute model). Similar results were obtained administering the NK1 receptor antagonist SSR140333 (3 and 10 mg/kg) for 5 days, starting the day after the induction of colitis. Intrarectal administration of DNBS four weeks after the first DNBS administration resulted in reactivation of colitis, with increases in macroscopic and histological damage scores and increase in MPO activity. Preventive treatment with SSR140333 10 mg/kg decreased macroscopic damage score, significantly reduced microscopic damage score but did not affect MPO activity. Conclusions: Treatment with SSR140333 significantly reduced intestinal damage in acute model of intestinal inflammation in rats. The NK1 receptor antagonist SSR140333 was also able to prevent relapse in experimental colitis. These results support the hypothesis of SP involvement in intestinal inflammation and indicate that NK receptor antagonists may have a therapeutic potential in inflammatory bowel disease.

Le Antichità di Bologna di Bartolomeo della Pugliola

For a long time, the work of a Franciscan Friar who had lived in Bologna and in Florence during the 13th and 14th centuries, Bartolomeo Della Pugliola, was thought to have been lost. Recent paleographic research, however, has affirmed that most of Della Pugliola’s work, although mixed into other authors, is contained in two manuscripts (1994 and 3843), currently kept at University Library in Bologna. Pugliola’s chronicle is central to Bolognese medieval literature, not only because it was the privileged source for the important work of Ramponis’ chronicle, but also because Bartolomeo della Pugliola’s sources are several significant works such as Jacopo Bianchetti’s lost writings and Pietro and Floriano Villolas’ chronicle (1163-1372). Ongoing historical studies and recent discoveries enabled me to reconstruct the historical chronology of Pugliola’s work as well as the Bolognese language between the 13th and 14th century The original purpose of my research was to add a linguistic commentary to the edition of the text in order to fill the gaps in medieval Bolognese language studies. In addition to being a reliable source, Pugliola’s chronicle was widely disseminated and became a sort of vulgate. The tradition of chronicle, through collation, allows the study of the language from a diachronic point of view. I therefore described all the linguistics phenomena related to phonetics, morphology and syntax in Pugliola’s text and I compared these results with variants in Villola’s and Ramponis’ chronicles. I also did likewise with another chronicle by a 16th century merchant, Friano Ubaldini, that I edited. This supplement helped to complete the Bolognese language outline from the 13th to the 16th century. In order to analize the data that I collected, I tried to approach them from a sociolinguistic point of view because each author represents a different variant of the language: closer to a scripta and the Florentine the language used by Pugliola, closer to the dialect spoken in Bologna the language used by Ubaldini. Differencies in handwriting especially show the models the authors try to reproduce or imitate. The glossary I added at the end of this study can help to understand these nuances with a number of examples.

Sviluppo di un tomografo multi-energy per lo studio pre-clinico di nuove metodiche diagnostiche finalizzate al riconoscimento precoce della patologia tumorale

A new multi-energy CT for small animals is being developed at the Physics Department of the University of Bologna, Italy. The system makes use of a set of quasi-monochromatic X-ray beams, with energy tunable in a range from 26 KeV to 72 KeV. These beams are produced by Bragg diffraction on a Highly Oriented Pyrolytic Graphite crystal. With quasi-monochromatic sources it is possible to perform multi-energy investigation in a more effective way, as compared with conventional X-ray tubes. Multi-energy techniques allow extracting physical information from the materials, such as effective atomic number, mass-thickness, density, that can be used to distinguish and quantitatively characterize the irradiated tissues. The aim of the system is the investigation and the development of new pre-clinic methods for the early detection of the tumors in small animals. An innovative technique, the Triple-Energy Radiography with Contrast Medium (TER), has been successfully implemented on our system. TER consist in combining a set of three quasi-monochromatic images of an object, in order to obtain a corresponding set of three single-tissue images, which are the mass-thickness map of three reference materials. TER can be applied to the quantitative mass-thickness-map reconstruction of a contrast medium, because it is able to remove completely the signal due to other tissues (i.e. the structural background noise). The technique is very sensitive to the contrast medium and is insensitive to the superposition of different materials. The method is a good candidate to the early detection of the tumor angiogenesis in mice. In this work we describe the tomographic system, with a particular focus on the quasi-monochromatic source. Moreover the TER method is presented with some preliminary results about small animal imaging.