1,721,753 research outputs found
Contestualizzazione nell’ambito sanitario pubblico nazionale
- Il Bilancio di missione delle Aziende sanitarie pubbliche della Regione Emilia-Romagna, in M. Biocca – R. Grilli – B. Riboldi, La governance nelle organizzazioni sanitarie, Franco Angeli, Milano, 2008;
- Contestualizzazione nell’ambito sanitario pubblico nazionale, in M. BIOCCA (a cura di), Bilancio di missione. Aziende responsabili si raccontano, Il Pensiero Scientifico Editore, Roma 2010. ISBN 978-88-490-0316-
Aggresome formation by anti-Ras intracellular scFv fragments. The fate of the antigen-antibody complex
Diverting the antigen from its normal intracellular location to other compartments in an antibody-mediated way represents a mode of action for intracellular antibodies [Cardinale, A., Lener, M., Messina, S., Cattaneo, A. & Biocca, S. (1998) FEBS Lett., 439, 197-202; Lener, M., Horn, I.R., Cardinale, A., Messina, S., Nielsen, U.B., Rybak, S.M., Hoogenboom, H.R., Cattaneo, A. & Biocca, S. (2000) Eur J Biochem. 267, 1196-205]. In the case of p21Ras, the sequestration of the antigen in aggregated structures in the cytoplasm of transfected cells leads to the inhibition of its biological function. We have further investigated the intracellular fate of the antigen-antibody complex by analyzing the effect of proteasome inhibitors on the formation and the intracellular localization of the aggregates. Overexpression of anti-Ras scFv fragments or inhibition of proteasomes activity leads to the formation of large perinuclear aggresomes formed of ubiquitinated-scFv fragments in which p21Ras is sequestered and degraded in an antibody-mediated way. Disruption of microtubules by nocodazole completely abrogates the accumulation of scFv fragments in a single aggresome and induces the dispersion of these structures in the periphery of the cell. Cotransfection of the GFP-scFv with a myc-tagged ubiquitin and colocalization with specific anti-proteasome antibodies indicate the recruitment of exogenous ubiquitin and proteasomes to the newly formed aggresomes. Taken together these results suggest that the intracellular antigen-antibody complex is naturally addressed to the ubiquitin-proteasome pathway and that the mechanism of ubiquitination does not inhibit the antibody binding properties and the capacity to block the antigen function
Evidence for proteasome dysfunction in cytotoxicity mediated by anti-Ras intracellular antibodies
Anti-Ras intracellular antibodies inhibit cell proliferation in vivo by sequestering the antigen and diverting it from its physiological location [Lener, M., Horn, I. R., Cardinale, A., Messina, S., Nielsen, U.B., Rybak, S.M., Hoogenboom, H.R., Cattaneo, A., Biocca, S. (2000) Eur. J. Biochem.267, 1196-1205]. Here we demonstrate that strongly aggregating single-chain antibody fragments (scFv), binding to Ras, induce apoptosis, and this effect is strictly related to the antibody-mediated aggregation of p21Ras. Proteasomes are quickly recruited to the newly formed aggregates, and their activity is strongly inhibited. This leads to the formation of aggresome-like structures, which become evident in the vast majority of apoptotic cells. A combination of anti-Ras scFv fragments with a nontoxic concentration of the proteasome inhibitor, lactacystin, markedly increases proteasome dysfunction and apoptosis. The dominant-negative H-ras (N17-H-ras), which is mostly soluble and does not induce aggresome formation or inhibit proteasome activity, only affects cell viability slightly. Together, these observations suggest a mechanism linking antibody-mediated Ras aggregation, impairment of the ubiquitin-proteasome system, and cytotoxicity
Storia del giornalismo contemporaneo (2)
Seconda parte di un corso E-learning sul giornalismo contemporaneo internazionale e lo sviluppo delle recenti tecnologie della comunicazione (radio, televisione, satellitare). Testi, immagini e domande (non incluse) sono dedicate alla storia dei media in America latina, Sudafrica, Medio oriente, Asia ed Europa. Il corso è stato realizzato presso il Centro di formazione giornalismo radiotelevisivo Rai e approvato dall'Ordine nazionale dei giornalisti per l'aggiornamento degli iscritti. Durata della video lezione: 35 min
The selection of intracellular antibodies
The intracellular expression of antibodies in mammalian cells is a strategy to inhibit the in vivo function of selected molecules but is limited by the unpredictable behaviour of antibodies when intracellularly expressed. Recent advances in the field of antibody expression in Escherichia coli show that the introduction of mutations can improve the properties of some antibody domains, but the general applicability of this approach to intracellular antibodies remains to be proved. As a complement to rational approaches, we describe selection schemes in which antibodies are selected on the basis of their performance in vivo as intracellular antibodies
Storia del Corriere della Sera, vol 3, Profilo storico. Dal fascismo alla Liberazione (1925-1945)
Il volume ricostruisce le vicende del Corriere della Sera dall'acquisizione della proprietà da parte della famiglia Crespi fino all'insurrezione del 25 aprile 1945. La ricerca è stata condotta sugli archivi del quotidiano e su documentazioni rinvenute presso l'Archivio Centrale dello Stato in Roma
Gene-Based Antibody Strategies for Prion Diseases
Prion diseases or transmissible spongiform encephalopathies (TSE) are a group of neurodegenerative and infectious disorders characterized by the conversion of a normal cellular protein PrPC into a pathological abnormally folded form, termed PrPSc. There are neither available therapies nor diagnostic tools for an early identification of individuals affected by these diseases. New gene-based antibody strategies are emerging as valuable therapeutic tools. Among these, intrabodies are chimeric molecules composed by recombinant antibody fragments fused to intracellular trafficking sequences, aimed at inhibiting, in vivo, the function of specific therapeutic targets. The advantage of intrabodies is that they can be selected against a precise epitope of target proteins, including protein-protein interaction sites and cytotoxic conformers (i.e., oligomeric and fibrillar assemblies). Herein, we address and discuss in vitro and in vivo applications of intrabodies in prion diseases, focussing on their therapeutic potential
The Silences of Dispossession
This book explores omissions, or silences, in previous investigations of agrarian transformations by foregrounding indigenous experiences of capitalist development. Providing a rich and detailed ethnographic study, Mercedes Biocca shows how capitalist processes are perceived, experienced, and either confronted or accepted depending on the different ways in which dispossession, resistance and negotiation have become embedded in the collective local memory. Challenging accounts that efface the agency of subalterns in shaping rural dynamics, and ignore the diversity of perspectives within indigenous groups, Biocca untangles the connections between global, national and local spatial scales in her analysis of accumulation by dispossession. Using two case studies, the Qom People in Pampa del Indio and the Moqoit people in Las Tolderías, she presents the main transformations that have taken place in the Argentine agricultural sector during the hegemony of post-neoliberalism while centring the perceptions and roles of subalterns within these transformations
El problema de las calificaciones en derecho internacional privado
Fil: Biocca, Stella Maris. Universidad de Buenos Aires. Facultad de Derecho. Cátedra Derecho Internacional Privado. Buenos Aires, Argentin
Combating protein misfolding and aggregation by intracellular antibodies
Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathology or impair the clearance mechanisms of misfolded aggregates. Aging is one of the risk factors associated to these events, and the clinical relevance of conformational disorders is growing dramatically, as they begin to reach epidemic proportions due to increases in mean lifespan. Currently, there are no effective strategies to slow or prevent these diseases. Intrabodies are promising therapeutic agents for the treatment of misfolding diseases, because of their virtually infinite ability to specifically recognize the different conformations of a protein, including pathological isoforms, and because they can be tarqeted to the potential sites of aggregation (both intra- and extracellular sites). These molecules can work as neutralizing agents bgainst amyloidogenic proteins by preventing their aggregation, and/or as molecular shunters of intracellular traffic by rerouting the protein from its potential aggregation site. The fast-developing field of recombinant antibody technology provides intrabodies with enhanced binding specificity and stability, together with lower immunogenicity, for use in a clinical setting. This review provides an update on the applications of intrabodies in misfolding diseases, with particular emphasis on an evaluation of their multipie and feasible modes of action. © 2008 Bentham Science Publishers Ltd
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