Violence, Death and Masculinity

A study of war and gender roles

Prolegomenon to a History of Travel

The author attempts to provide a definition of travel by comparing it with the instinctive migration of animals and birds and viewing its changes over time. As a study of motion voluntarily undertaken, a history of travel can contribute to a better understanding of human being

15. As perdas da historía

As perdas da história Como consegue um povo indígena, em meio às vicissitudes do contato interétnico que provocam sua dispersão e dizimação, gerar e preservar uma identidade coletiva? O ciclo mítico de Unurato responde a tal pergunta, introduzindo a figura do branco no seu referencial simbólico e revelando como, nesse processo, os Arapaço reconstroem sua auto-imagem no palco interétnico. O mito será aqui colocado em perspectiva histórica, numa tentativa de mostrar como o seu sistema de signif..

Characterization of the Prion Protein Binding Properties of Antisense Oligonucleotides

Antisense oligonucleotides (ASOs) designed to lower prion protein (PrP) expression in the brain through RNase H1-mediated degradation of PrP RNA are in development as prion disease therapeutics. ASOs were previously reported to sequence-independently interact with PrP and inhibit prion accumulation in cell culture, yet in vivo studies using a new generation of ASOs found that only PrP-lowering sequences were effective at extending survival. Cerebrospinal fluid (CSF) PrP has been proposed as a pharmacodynamic biomarker for trials of such ASOs, but is only interpretable if PrP lowering is indeed the relevant mechanism of action in vivo and if measurement of PrP is unconfounded by any PrP–ASO interaction. Here, we examine the PrP-binding and antiprion properties of ASOs in vitro and in cell culture. Binding parameters determined by isothermal titration calorimetry were similar across all ASOs tested, indicating that ASOs of various chemistries bind full-length recombinant PrP with low- to mid-nanomolar affinity in a sequence-independent manner. Nuclear magnetic resonance, dynamic light scattering, and visual inspection of ASO–PrP mixtures suggested, however, that this interaction is characterized by the formation of large aggregates, a conclusion further supported by the salt dependence of the affinity measured by isothermal titration calorimetry. Sequence-independent inhibition of prion accumulation in cell culture was observed. The inefficacy of non-PrP-lowering ASOs against prion disease in vivo may be because their apparent activity in vitro is an artifact of aggregation, or because the concentration of ASOs in relevant compartments within the central nervous system (CNS) quickly drops below the effective concentration for sequence-independent antiprion activity after bolus dosing into CSF. Measurements of PrP concentration in human CSF were not impacted by the addition of ASO. These findings support the further development of PrP-lowering ASOs and of CSF PrP as a pharmacodynamic biomarker

San Pietroburgo andata e ritorno. Riflessioni sul reportage di viaggio e su Viaggi di Russia di Francesco Algarotti

As a result of a travel experience in Russia in 1739, Viaggi di Russia by Francesco Algarotti, published in its final version in 1764, represents a text of certain interest in the panorama of studies related to travel literature and its dynamics. The genre of travel reportage, much frequented by twentieth-century Italian writers after the encounter between literature and journalism on the Third page of Italian newspapers, finds in Algarotti a sure antecedent: despite the clear literary intent of the writing back from St. Petersburg, in the reportage we can find elements of interest also in relation to the travel reports of twentieth-century writers-journalists