A new Near InfraRed (NIR) fluorescent chemosensor for metal ions and anions is herein presented. The fluorophore is based on a styrylflavylium dye, a synthetic analogue of the natural anthocyanin family, with a di-(2-picolyl)amine (DPA) moiety as the metal chelating unit. The substitution pattern of the styrylflavylium core (with tertiary amines on positions 7 and 4′) shifts the optical properties of the dye towards the NIR region of the electronic spectra, due to a strong push-pull character over the π-conjugated system. The NIR chemosensor is highly sensitive to the presence of Zn2+, which induces a strong CHelation Enhanced Fluorescence (CHEF) effect upon binding to the DPA unit (2.7 fold increase). The strongest competing ion is Cu2+, with a complete fluorescence quenching, while other metals induce lower responses on the optical properties of the chemosensor. Subsequent anion screening of the Zn2+-chemosensor coordination compound has demonstrated a distinct selectivity towards adenosine 5′-triphosphate (ATP) and adenosine 5′-diphosphate (ADP), with high association constants (K ~ 106 M−1) and a strong CHEF effect (2.4 and 2.9 fold fluorescence increase for ATP and ADP, respectively). Intracellular studies with the Zn2+-complexed sensor showed strong luminescence in the cellular membrane of Gram– bacteria (E. coli) and mitochondrial membrane of mammalian cells (A659), which highlights its possible application for intracellular labelling.
This article focuses on the literary landscape of Monsanto. It confronts the discourse produced by the writer, Fernando Namora (1819-1989)—a pioneer of the Neo-Realistic literature in Portugal—and the literary production of other contemporary authors related with the ideological bases of “Estado Novo” (“New State”), the dictatorial regime that held the government in Portugal from 1933 to 1974. In the writings analysed, the representation of the landscapes of Monsanto entails powerful ideological messages. For Namora, the village was a “stone vessel,” a metaphor about the hard life of its inhabitants, victims of social injustices and lacking of resources. For the “Estado Novo,” that place was the symbol of the national identity (“the most Portuguese village,” as was stated in 1938). The metaphors of the stone, the strong substrata and the raw material used for shelters, stressed the value of preservation of Tradition, History, Religion and Work. Although very different, both discourses attach great value to the productive and dominated rural landscape of Monsanto, and to the human role in the transformation of its soil. At the present time, even if population has decreased drastically and agriculture has been abandoned, local authorities and tourist agents alike try to conciliate the “stone vessel” with “the most Portuguese village.” In this context, the options for the management and valorisation of the landscape of Monsanto shall be discussed. Resumen En este artículo se reflexiona sobre el paisaje literario de Monsanto, confrontando el discurso producido por el escritor Fernando Namora (1919-1989), precursor de la literatura neo-realista en Portugal, con el de otros autores contemporáneos, asociados directa o indirectamente a las bases ideológicas del “Estado Novo” (“Estado Nuevo”), el régimen dictatorial de Portugal que se extendió desde 1933 hasta 1974. En las obras analizadas, las representaciones del paisaje de Monsanto encierran poderosos mensajes ideológicos. Según Namora, el pueblo era una “nave de piedra”, metáfora de la dureza de la vida de los aldeanos, víctimas de las injusticias sociales y de la escasez de recursos. Para el “Estado Novo”, era un símbolo de la identidad nacional (“el pueblo más portugués”, tal y como quedó formulado en 1938); la metáfora de la roca, el substrato firme y la materia prima usados para el abrigo de la población, contribuían a la conservación de los valores de la Tradición, de la Historia, de la Religión y del Trabajo. Aunque distintos, ambos discursos valoran el paisaje agrícola, dominado y hecho productivo, y el rol de la población en el proceso de transformación del territorio. En la actualidad, pese al fuerte menguar de la población y al abandono de la agricultura, las autoridades locales y los agentes turísticos asumen un paisaje de referencia e intentan conciliar la “nave de piedra” con “el pueblo más portugués”. En este contexto, se debaten las opciones de gestión y valoración del paisaje de Monsanto.
Effective diagnosis and treatment in cancer is a barrier for the development of personalized medicine, mostly due to tumor heterogeneity. In the particular case of gliomas, highly heterogeneous brain tumors at the histological, cellular and molecular levels, and exhibiting poor prognosis, the mechanisms behind tumor heterogeneity and progression remain poorly understood. The recent advances in biomedical high-throughput technologies have allowed the generation of large amounts of molecular information from the patients that combined with statistical and machine learning techniques can be used for the definition of glioma subtypes and targeted therapies, an invaluable contribution to disease understanding and effective management.In this work sparse and robust sparse logistic regression models with the elastic net penalty were applied to glioma RNA-seq data from The Cancer Genome Atlas (TCGA), to identify relevant transcriptomic features in the separation between lower-grade glioma (LGG) subtypes and identify putative outlying observations. In general, all classification models yielded good accuracies, selecting different sets of genes. Among the genes selected by the models, TXNDC12, TOMM20, PKIA, CARD8 and TAF12 have been reported as genes with relevant role in glioma development and progression. This highlights the suitability of the present approach to disclose relevant genes and fosters the biological validation of non-reported genes.
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