BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population.

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor-triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

Errata du "Dictionnaire de l'Académie française" ou Remarques critiques sur les irrégularités qu'il présente : avec l'indication de certaines règles à établir ([Reprod.]) / par B. Pautex,...

Collection : Archives de la linguistique française ; 311

René-Théophile-Hyacinthe Laennec (1781-1826) and the description of metastatic pulmonary melanoma.

In 19th century, the anatomo-clinical school of Paris linked clinical signs with anatomical lesions establishing clinical medicine. One of the most enlightened promoters of this method was the French physician René-Théophile-Hyacinthe Laennec, known as the inventor of stethoscope. In our article, we reveal his work on pulmonary melanoma.

La "imatge" de la caverna i la temptació constant de corregir Plató: Benjamin Jowett com a exemple

[cat] Les traduccions dels primers capítols del llibre VII de la República de Plató on apareix la famosa imatge de la caverna, εἰκών, presenten una sorprenent i intrigant varietat interpretativa: “al·legoria���, “mite”, “faula���, “paràbola���, “símil”, “comparació”... Aquest article, prenent com a exemple la notable fidelitat al text del traductor victorià de Plató, B. Jowett, i mitjançant una anàlisi rigorosa dels termes que acompanyen la imatge, manté la necessitat de no interpretar ni corregir en aquest cas el gran filòsof idealista o “ideocèntric”, assenyalant alhora, si el capteniment filològic és un altre, les contradiccions resultants i l’ús d’algun terme aliè al lèxic platònic com ara “al·legoria���.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Continuidade ou ruptura? Uma análise de alguns aspectos da filosofia social de John Stuart Mill, Alfred Marshall e John Maynard Keynes

O artigo argumenta que é possível se falar em uma 'tradição' no campo de filosofia social e econômica unindo as obras de J.S. Mill e Alfred Marshall e J.M. Keynes. Essa 'tradição' pode ser caracterizada pelas seguintes concepções: (a) pela rejeição moral aos valores aquisitivos do capitalismo; (b) pela visão de que o sistema capitalista seria incapaz de resolver de forma espontânea as questões das desigualdades de renda e riqueza e da pobreza; (c) pela ideia de que, por uma questão de garantia de liberdade e da diversidade, além de por questões de eficiência econômica, dever-se-ia deixar a iniciativa individual agir livremente nas esferas em que é capaz de engendrar bons resultados, mas que o Estado deveria intervir, quando essa falha, atuando em benefício da coletividade; (d) pela crença de que seria possível melhorar significativamente esse sistema por meio de mudanças pontuais e graduais.

Annales de l'École libre des sciences politiques : recueil trimestriel / publié avec la collaboration des professeurs et des anciens élèves de l'école ; comité de rédaction M. Emile Boutmy,... M. Léon Say,... M. Alfred de Foville,...

1896 (A11).