La Costituzione Invisibile - Costituzione e democrazia alla prova dell’emergenza: riflessioni di un melanconico

RIASSUNTO: L'articolo prende le mosse da una risalente analisi di Pier Paolo Pasolini sul pericolo che incombe non ravvisato sulle democrazie occidentali e, a partire dal problema della gestione costituzionale e giuridica dell'emergenza covid-19 e dalle prospettive di considerarla una ‘occasione’ per l'attivazione della quarta rivoluzione industriale digitale, si interroga sul rapporto storico intercorrente tra democrazie e dittatura, e sull’eclisse che sembra colpire lo stesso rapporto costituzione (libertà) – democrazia in nome di una torsione biopolitica della nozione di vita

L’ipotesi Tocqueville

O presente ensaio reflete, a partir do debate na Assembleia Constituinte italiana (1946-1948) e da análise acerca da declaração do estado de exceção realizada pela doutrina constitucional italiana do segundo novecentos, sobre o tema da limitação dos direitos constitucionais invioláveis na gestão governamental da crise covid-19. Partindo dessa questão expande o olhar para observar as origens sistêmicas dos procedimentos de tipo fundamentalmente administrativo postos em funcionamento. Recuperando uma declinação da democracia “sem liberdade”, preconizada por autores como Tocqueville e Einaudi, como possível resultado de uma democracia que perca a sua ligação com o rule of law, analisa-se o possível desenvolvimento de democracias de molde ocidental na direção de modelos de Security State, não mais fundados no combate ao terrorismo, mas no risco sanitário como horizonte absorvente.O presente ensaio reflete, a partir do debate na Assembleia Constituinte italiana (1946-1948) e da análise acerca da declaração do estado de exceção realizada pela doutrina constitucional italiana do segundo novecentos, sobre o tema da limitação dos direitos constitucionais invioláveis na gestão governamental da crise covid-19. Partindo dessa questão expande o olhar para observar as origens sistêmicas dos procedimentos de tipo fundamentalmente administrativo postos em funcionamento. Recuperando uma declinação da democracia “sem liberdade”, preconizada por autores como Tocqueville e Einaudi, como possível resultado de uma democracia que perca a sua ligação com o rule of law, analisa-se o possível desenvolvimento de democracias de molde ocidental na direção de modelos de Security State, não mais fundados no combate ao terrorismo, mas no risco sanitário como horizonte absorvente

Direito comum

Resum

Mechanisms of HIV-1 Nucleocapsid Protein Inhibition by Lysyl-Peptidyl-Anthraquinone Conjugates

The Nucleocapsid protein NCp7 (NC) is a nucleic acid chaperone responsible for essential steps of the HIV-1 life cycle and an attractive candidate for drug development. NC destabilizes nucleic acid structures and promotes the formation of annealed substrates for HIV-1 reverse transcription elongation. Short helical nucleic acid segments bordered by bulges and loops, such as the Trans-Activation Response element (TAR) of HIV-1 and its complementary sequence (cTAR), are nucleation elements for helix destabilization by NC and also preferred recognition sites for threading intercalators. Inspired by these observations, we have recently demonstrated that 2,6-disubstituted peptidylanthraquinone-conjugates inhibit the chaperone activities of recombinant NC in vitro, and that inhibition correlates with the stabilization of TAR and cTAR stem-loop structures. We describe here enhanced NC inhibitory activity by novel conjugates that exhibit longer peptidyl chains ending with a conserved Nterminal lysine. Their efficient inhibition of TAR/cTAR annealing mediated by NC originates from the combination of at least three different mechanisms, namely, their stabilizing effects on nucleic acids dynamics by threading intercalation, their ability to target TAR RNA substrate leading to a direct competition with the protein for the same binding sites on TAR, and, finally, their effective binding to the NC protein. Our results suggest that these molecules may represent the stepping-stone for the future development of NC-inhibitors capable of targeting the protein itself and its recognition site in RNA

Molecular simulations of SSTR2 dynamics and interaction with ligands

The cyclic peptide hormone somatostatin regulates physiological processes involved in growth and metabolism, through its binding to G-protein coupled somatostatin receptors. The isoform 2 (SSTR2) is of particular relevance for the therapy of neuroendocrine tumours for which different analogues to somatostatin are currently in clinical use. We present an extensive and systematic computational study on the dynamics of SSTR2 in three different states: active agonist-bound, inactive antagonist-bound and apo inactive. We exploited the recent burst of SSTR2 experimental structures to perform μs-long multi-copy molecular dynamics simulations to sample conformational changes of the receptor and rationalize its binding to different ligands (the agonists somatostatin and octreotide, and the antagonist CYN154806). Our findings suggest that the apo form is more flexible compared to the holo ones, and confirm that the extracellular loop 2 closes upon the agonist octreotide but not upon the antagonist CYN154806. Based on interaction fingerprint analyses and free energy calculations, we found that all peptides similarly interact with residues buried into the binding pocket. Conversely, specific patterns of interactions are found with residues located in the external portion of the pocket, at the basis of the extracellular loops, particularly distinguishing the agonists from the antagonist. This study will help in the design of new somatostatin-based compounds for theranostics of neuroendocrine tumours

Development of interactive algorithm for clinical management of acute events related to sickle cell disease in emergency department

Sickle cell disease (SCD ORPHA232; OMIM 603903) is a rare hereditary red cell disorder, which global distribution is changed in the last decade due to immigration-fluxes from endemic areas to Western-countries. One of the main clinical manifestations of SCD are the acute painful vaso-occlusive crisis, which cause frequent accesses of SCD patients to the emergency departments (EDs). This has generated the requirement of feasible tools for emergency givers. In the context of the scientific-Italian-Society for the study of Thalassemias and Hemoglobinopathies (SITE), we developed an algorithm with interactive windows to guide physicians in managing SCD patients in EDs

Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)

The understanding of Earth’s biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E. maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E. maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E. maximus