Ly9 (CD229) Cell-Surface Receptor is Crucial for the Development of Spontaneous Autoantibody Production to Nuclear Antigens

The Signaling Lymphocyte Activation Molecule Family (SLAMF) genes, which encode cell-surface receptors that modulate innate and adaptive immune responses, lay within a genomic region of human and mouse chromosome 1 that confers a predisposition for the development of systemic lupus erythematosus (SLE). Herein, we demonstrate that the SLAMF member Ly9 arises as a novel receptor contributing to the reinforcement of tolerance. Specifically, Ly9-deficient mice spontaneously developed features of systemic autoimmunity such as the production of anti-nuclear antibodies (ANA), -dsDNA, and -nucleosome autoantibodies, independently of genetic background [(B6.129) or (BALB/c.129)]. In aged (10- to 12-month-old) Ly9−/− mice key cell subsets implicated in autoimmunity were expanded, e.g., T follicular helper (Tfh) as well as germinal center (GC) B cells. More importantly, in vitro functional experiments showed that Ly9 acts as an inhibitory receptor of IFN-γ producing CD4+ T cells. Taken together, our findings reveal that the Ly9 receptor triggers cell intrinsic safeguarding mechanisms to prevent a breach of tolerance, emerging as a new non-redundant inhibitory cell-surface receptor capable of disabling autoantibody responses

Asympyotic behavior of Musielak-Orlicz-Sobolev modulars

In this article we study the asymptotic behavior of anisotropic nonlocal nonstandard growth seminorms and modulars as the fractional parameter goes to 1. This gives a so-called Bourgain-Brezis-Mironescu type formula for a very general family of functionals. In the particu\-lar case of fractional Sobolev spaces with variable exponent, we point out that our proof asks for a weaker regularity of the exponent than the considered in previous articles

Librarians in times of cyberculture: reflections on professional performance and library practices

Este artigo apresenta parte dos resultados de pesquisa de uma dissertação na qual busca-se aprofundar as reflexões sobre as práticas dos bibliotecários e identificar suas percepções e sentidos sobre a atuação profissional e sobre a biblioteca universitária no contexto da cibercultura. O estudo foi realizado em uma biblioteca universitária da área médica e nele apresentam-se a trajetória e as características dessa biblioteca e identificam-se, com base em entrevistas semiestruturadas realizadas com oito bibliotecárias atuantes ou aposentadas, os sentidos atribuídos às práticas bibliotecárias. Percebe-se nas narrativas uma constante busca por reconhecimento e valorização da profissão, assim como a preocupação em manter a frequência dos usuários ao espaço físico da biblioteca estudada. Dentre as modificações percebidas nessa atuação, nota-se que o sentido de “mediador” passa a dar espaço ao sentido de “educador” e a postura de “esperar o usuário” passa a dar lugar a de “buscar o usuário”, o que demonstra uma inquietação com relação ao futuro da biblioteca e da atuação do bibliotecário. Assim como, identificam-se sentidos que podem indicar estratégias de manutenção da cultura profissional e da permanência no mercado de trabalho.It is the third part of the epistemological demarcations that configure the citation studies in the contemporaneity. It is based on the assumption that social and cultural contexts are vital in the development of citation studies, since they formalize the relationship between production and citation practices. It aims to propose the initial epistemological design for a sociocultural conception of the citations, with emphasis on the revelation of the influences of the multiple contexts in the processes of production and citation of the scientists. It presents and discusses the scientific components for the sociocultural conception of citations, complementary in nature to the theories of citations. It suggests an epistemological matrix for citation studies and also a multidimensional analytical model for future investigations. It concludes that the sociocultural conception can be applied methodologically, in a complementary way, in researches that problematize the established relationship between production and citation

Ly9 (CD229) cell surface receptor is crucial for the development of spontaneous autoantibody production to nuclear antigens

The Signaling Lymphocyte Activation Molecule Family (SLAMF) genes, which encode cell-surface receptors that modulate innate and adaptive immune responses, lay within a genomic region of human and mouse chromosome 1 that confers a predisposition for the development of systemic lupus erythematosus (SLE). Herein, we demonstrate that the SLAMF member Ly9 arises as a novel receptor contributing to the reinforcement of tolerance. Specifically, Ly9-deficient mice spontaneously developed features of systemic autoimmunity such as the production of anti-nuclear antibodies (ANA), -dsDNA, and -nucleosome autoantibodies, independently of genetic background [(B6.129) or (BALB/c.129)]. In aged (10- to 12-month-old) Ly9 (-/-) mice key cell subsets implicated in autoimmunity were expanded, e.g., T follicular helper (Tfh) as well as germinal center (GC) B cells. More importantly, in vitro functional experiments showed that Ly9 acts as an inhibitory receptor of IFN-γ producing CD4(+) T cells. Taken together, our findings reveal that the Ly9 receptor triggers cell intrinsic safeguarding mechanisms to prevent a breach of tolerance, emerging as a new non-redundant inhibitory cell-surface receptor capable of disabling autoantibody responses

La subida al Calvario de Scipione Pulzone para Marcantonio Colonna

This article presents the <i>Way to Calvary</i> painted by Pulzone in 1581-83 for Marcantonio Colonna, then viceroy of Sicily. The latter sent it as a gift to Mateo Vázquez, secretary to Philip II, in testimony of their friendship and to thank him for supporting the ecclesiastical career of his son Ascanio, who delivered the painting in Madrid. When Vázquez died, it was inherited by his homonymous nephew, archdeacon of Carmona, who took it to Seville where Pacheco described it in the early 17<sup>th</sup> century. The author examines the painting’s iconography in connexion with Raphael’s and Sebastiano del Piombo’s models, as well as other representations in Roman painting of the period. He also points out that cardinal Ferdinando de’ Medici intended to send to Spain the autograph replica made for him; this confirms that Pulzone’s picture seems to have perfectly met the Spanish predilection, well-known in Rome, for the pathetic in religious art.<br><br>Este artículo presenta la <i>Subida al Calvario</i> que Pulzone pintó en 1581-83 para Marcantonio Colonna, entonces virrey de Sicilia. Al poco de recibirlo, el comitente se lo regaló a Mateo Vázquez, secretario de Felipe II, en testimonio de amistad y para agradecerle el apoyo a la carrera eclesiástica de su hijo Ascanio. A la muerte de Vázquez lo heredó su sobrino homónimo, arcediano de Carmona; éste lo llevó a Sevilla donde a comienzos del siglo XVII lo describió Pacheco. Amén de examinar la iconografía en conexión con los modelos de Sebastiano del Piombo y Rafael y las otras representaciones del tema en la pintura romana coetánea, se señala que también el cardenal Ferdinando de’ Medici pensó enviar a España la réplica que el mismo autor le había hecho: esto confirma que la obra de Pulzone pareció poder satisfacer perfectamente la predilección española, muy bien conocida en Roma, por el patetismo en el arte religioso

Special issue: Advances in Engineering Networks

[EN] This special issue of the International Journal of Production Management and Engineering is dedicated on the most recent and relevant research, theories and practices in Industrial Engineering and Operations Management presented at the 12th International Conference on Industrial Engineering and Industrial Management and XXII Congreso de Ingeniería de Organización - CIO18.De Castro, R.; Gimenez, G.; Mula, J.; Boza, A.; Cuenca, L.; Gómez-Gasquet, P.; Vicens-Salort, E. (2019). Special issue: Advances in Engineering Networks. International Journal of Production Management and Engineering. 7(Número Especial):63-64. https://doi.org/10.4995/ijpme.2019.11901SWORD63647Número Especia

Asserta medica ... ad mente[m] ... Hipps. apertendam publicae disputationi

Cartel anunciador de la disertaciónCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2016Fecha en tít. : 1780Texto enmarcado en grab. calc.Grab. calc. de águila bicéfala:"D. Joachimus Rodriguez de Munera, Inventor. Alagarda d. et sculp. Oriolae. P.C. Tip.

Exploring Biginelli-based scaffolds as A2B adenosine receptor antagonists: Unveiling novel structure-activity relationship trends, lead compounds, and potent colorectal anticancer agents

Antagonists of the A(2B) adenosine receptor have recently emerged as targeted anticancer agents and immune checkpoint inhibitors within the realm of cancer immunotherapy. This study presents a comprehensive evaluation of novel Biginelli-assembled pyrimidine chemotypes, including mono-, bi-, and tricyclic derivatives, as A(2B)AR antagonists. We conducted a comprehensive examination of the adenosinergic profile (both binding and functional) of a large compound library consisting of 168 compounds. This approach unveiled original lead compounds and enabled the identification of novel structure-activity relationship (SAR) trends, which were supported by extensive computational studies, including quantum mechanical calculations and free energy perturbation (FEP) analysis. In total, 25 molecules showed attractive affinity (K-i < 100 nM) and outstanding selectivity for A(2B)AR. From these, five molecules corresponding to the new benzothiazole scaffold were below the K-i < 10 nM threshold, in addition to a novel dual A(2A)/A(2B) antagonist. The most potent compounds, and the dual antagonist, showed enantiospecific recognition in the A(2B)AR. Two A(2B)AR selective antagonists and the dual A(2A)AR/A(2B)AR antagonist reported in this study were assessed for their impact on colorectal cancer cell lines. The results revealed a significant and dose-dependent reduction in cell proliferation. Notably, the A(2B)AR antagonists exhibited remarkable specificity, as they did not impede the proliferation of non-tumoral cell lines. These findings support the efficacy and potential that A(2B)AR antagonists as valuable candidates for cancer therapy, but also that they can effectively complement strategies involving A(2A)AR antagonism in the context of immune checkpoint inhibition