The exchange market and businessmen in Barcelona during the war between Alfonso the Magnanimous and the Florentine Republic

La metà del secolo XV fu per la Corona d’Aragona e specialmente per Barcellona un periodo complicato: Alfonso V era impegnato nelle guerre italiane, in particolare contro Firenze e Milano, Genova e Venezia; il Regno di Napoli era stato annesso all’Unione, e richiedeva sforzi importanti per il suo mantenimento; allo stesso tempo dalla capitale catalana provenivano richieste di apertura “democratica” del Consiglio dei Cento, che portavano a un’evidente instabilità interna, frutto in parte di una dimostrata crisi monetaria, dovuta anche alla scarsa capacità di governo dell’economia. Nonostante ciò, i mercanti, gli armatori e i banchieri continuarono a cercare di portare avanti i propri interessi economici nel Mediterraneo, anche servendosi delle istituzioni di natura corporativa, come il Consolato del mare. Attraverso l’analisi di alcuni registri di protesti di lettere di cambio gestiti dal notaio del Consolato barcellonese, si cercherà di mettere in luce l’evoluzione delle reti mercantili-finanziarie catalane, in particolare lungo la rotta meridionale italiana. Lo studio non avrà l’obiettivo di analizzare l’uso tecnico dello strumento cambiario, ma quello di portare alla luce strategie e protagonisti del processo di inserimento del capitale mercantile e finanziario in Italia durante il regno di Alfonso il Magnanimo e in special modo durante la guerra contro Firenze. Emergeranno, così, i nomi di quelle persone che furono le protagoniste dei grandi e quotidiani spostamenti di denaro fra i centri politico-commerciali del Commonwealth catalanoaragonese. Si tenterà una prima ricostruzione delle loro attività e dei loro movimenti, nonché delle connessioni con i più importanti operatori del sistema finanziario europeo, ovvero i toscani.The middle of the 15th century was a complicated period for the Crown of Aragon and especially for Barcelona: Alfonso V was engaged in the Italian wars, particularly against Florence and Milan, Genoa and Venice; the Kingdom of Naples had been annexed to the Crown, and required major efforts for its maintenance; at the same time, from the Catalan capital, demands for a “democratic” opening of the Council of Hundred were coming, which led to an evident internal instability, partly resulted from a proven monetary crisis and from the scarce capacity to manage the economy. Despite this, merchants, ship owners and bankers continued to advance their economic interests in the Mediterranean, even using institutions with a corporative nature, such as the Consulate of the sea. By analysing some registers containing protests of bills of exchange managed by the notary of the Consulate of Barcelona, an attempt will be made to highlight the evolution of Catalan mercantile-financial networks, particularly along the route to Southern Italy. The study will not analyse the technical use of the instrument of exchange, its aim will be bringing to light the strategies and protagonists in the process of insertion of mercantile and financial capital in Italy during the reign of Alfonso the Magnanimous and especially during the war against Florence. With this approach, the names of those people who were the protagonists of the large, daily movements of money between the political and commercial centres of the Catalan-Aragonese Commonwealth will emerge. An initial reconstruction of their activities and movements will be attempted, as well as connections with the most important operators in the European financial system, i. e. the Tuscans

Clinical global impression-severity score as a reliable measure for routine evaluation of remission in schizophrenia and schizoaffective disorders

Aims: This study aimed to compare the performance of Positive and Negative Syndrome Scale (PANSS) symptom severity criteria established by the Remission in Schizophrenia Working Group (RSWG) with criteria based on Clinical Global Impression (CGI) severity score. The 6-month duration criterion was not taken into consideration. Methods: A convenience sample of 112 chronic psychotic outpatients was examined. Symptomatic remission was evaluated according to RSWG severity criterion and to a severity criterion indicated by the overall score obtained at CGI-Schizophrenia (CGI-SCH) rating scale (≤3) (CGI-S). Results: Clinical remission rates of 50% and 49.1%, respectively, were given by RSWG and CGI-S, with a significant level of agreement between the two criteria in identifying remitted and non-remitted cases. Mean scores at CGI-SCH and PANSS scales were significantly higher among remitters, independent of the remission criteria adopted. Measures of cognitive functioning were largely independent of clinical remission evaluated according to both RSWG and CGI-S. When applying RSWG and CGI-S criteria, the rates of overall good functioning yielded by Personal and Social Performance scale (PSP) were 32.1% and 32.7%, respectively, while the mean scores at PSP scale differed significantly between remitted and non-remitted patients, independent of criteria adopted. The proportion of patients judged to be in a state of well-being on Social Well-Being Under Neuroleptics-Short Version scale (SWN-K) were, respectively, 66.1% and 74.5% among remitters according to RSWG and CGI-S; the mean scores at the SWN scale were significantly higher only among remitters according to CGI-S criteria. Conclusions: CGI severity criteria may represent a valid and user-friendly alternative for use in identifying patients in remission, particularly in routine clinical practic

Dynamics of soluble immune mediators in COVID-19 patients from an Argentinean cohort with moderate and severe symptoms

The cytokine storm, a form of systemic inflammatory response syndrome, is one of the most dreadful complications that can occur during COVID-19. The severity of infection is associated at different levels of these immune mediators and many molecules are considered marker of COVID mortality. Because of its central role in the pathogenesis of SARS-CoV-2 infection, the cytokine storm have become a therapeutic target in the treatment of COVID-19 patients.In this work, we aimed at studying the concentration of different pro- and anti-inflammatory cytokines in a cohort of COVID-19 patients from Córdoba (Argentine). The immunological reaction triggered by infection with SARS-CoV-2 mobilizes numerous cytokines, mainly of proinflammatory character. Changes in their levels are associated with the presence of the disease and with a more severe prognosis. Although our data have similarities with those in international reports, the complete profiling of different parameters (cytokine/chemokines, risk factors, epidemiological and clinical characteristics) in the local cases add value by identifying particularities that may be relevant for the management and prognosis during SARS-CoV2 infection in Argentine.Fil: Almada, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Angiolin, Sofia C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Dho, Nicolás. Universidad Nacional de Córdoba; ArgentinaFil: Dutto, Jeremias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gazzon, Yamila. Universidad Nacional de Córdoba; ArgentinaFil: Manzone, Clarisa. Universidad Nacional de Córdoba; ArgentinaFil: Marin, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Morón, Gabriel. Universidad Nacional de Córdoba; ArgentinaFil: Amezcua Vesely, Carolina. Universidad Nacional de Córdoba; ArgentinaFil: Ana, Yamile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Chiapello, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fozzatt, Laura. Universidad Nacional de Córdoba; ArgentinaFil: Icely, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Mena, Cristian Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Motrán, Cristina. Universidad Nacional de Córdoba; ArgentinaFil: Rodríguez Galán, Cecilia. Universidad Nacional de Córdoba; ArgentinaFil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Viano, María Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bertone, M.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Abiega, Claudio Daniel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Escudero, Daiana Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Privado Universitario de Córdoba; ArgentinaFil: Kahn, Adrian Mario. Hospital Privado Universitario de Córdoba; ArgentinaFil: Caeiro, Juan Pablo. Hospital Privado Universitario de Córdoba; ArgentinaFil: Arroyo, Daniela Soledad. Hospital Privado Universitario de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maletto, Belkys Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sotomayor, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaLXVI reunión anual de la sociedad argentina de investigación clínica (saic), LXIX reunión anual de la sociedad argentina de inmunología (sai), LIII reunión anual de la asociación argentina de farmacología experimental (aafe), XI reunión anual de la asociación argentina de nanomedicinas (nanomed-ar)Buenos AiresArgentinaSociedad Argentina de Inmunologí

Phosphorylation controls autoinhibition of cytoplasmic linker protein-170

Author Posting. © American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036.Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.This work was supported by National Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences and RFBP grant 05-04-4915 (to E.S.N.)

COVID-19 patients display changes in lymphocyte subsets with a higher frequency of dysfunctional CD8lo T cells associated with disease severity

This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3+ T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4+ T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB+ T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8+ T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8hi and CD8lo T cells within the CD8+ population in HD are similar, a significant increase was observed in CD8lo T cell frequency in COVID-19 patients. CD8lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8hi T cells. Interestingly, the frequency of CD8lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8hi/CD8lo index helped to significantly improve the patient’s clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8hi/CD8lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients