'Otro': consideraciones a favor de su no inclusión en la categoría de determinante

En el español actual otro presenta propiedades complejas y, como en otros idiomas, la contribución que esta pieza léxica aporta al significado del sintagma nominal está relacionada con el contexto comunicativo: una expresión nominal modificada por otro denota una o más entidades que se diferencian o se suman a otra u otras entidades introducidas precedentemente en el contexto o conocidas ya. En este trabajo se estudia las propiedades interpretativas y sintácticas de otro según una perspectiva comparativa con otras lenguas románicas, en particular, el catalán, el francés y el italiano. Se argumentará que en el español actual este elemento no puede analizarse como un determinante, sino como un adjetivo con propiedades funcionales cuando aparece en contextos definidos (referenciales) y como un cuantificador cuando aparece en contextos indefinidos (existenciales). Esto explicaría la omisión de un determinante indefinido. Además, adoptando el enfoque cartográfico y extendiendo al español actual la propuesta de Cinque (2015) sobre "otro" en italiano y otros idiomas, se argumentará que las dos interpretaciones que otro expresa, es decir, la interpretación de alteridad y la interpretación aditiva, están asociadas, en contextos referenciales, a dos posiciones diferentes dentro de la estructura interna de la expresión nominal. Se mostrará asimismo que cuando otro es cuantificador puede combinarse con otros cuantificadores existenciales, dando lugar a formas complejas

Modulation of Oxidative Status by Normoxia and Hypoxia on Cultures of Human Dermal Fibroblasts: How Does It Affect Cell Aging?

Reactive oxygen species (ROS) production in the skin is among the highest compared to other organs, and a clear correlation exists between ROS production and skin aging. Many attempts are underway to reduce oxidative stress in the skin by topical treatment or supplementation with antioxidants/cosmeceuticals, and cultures of human dermal fibroblasts (HDF) are widely used for these studies. Here, we examined the influence of oxygen tension on cell aging in HDF and how this impacted ROS production, the enzymatic and nonenzymatic antioxidant response system, and the efficacy of this defense system in limiting DNA damage and in modulating gene expression of proteins involved in the extracellular matrix, linked to skin aging. We investigated a selection of parameters that represent and reflect the behavior of cellular responses to aging and oxygen tension. Serial passaging of HDF under normoxia (21%) and hypoxia (5%) leads to cell aging as confirmed by β-galactosidase activity, p16 expression, and proliferation rate. However, in HDF under 21% O2, markers of aging were significantly increased compared to those under 5% O2 at matched cell passages despite having lower levels of intracellular ROS and higher levels of CoQ10, total GSH, SOD1, SOD3, and mitochondrial superoxide anion. miRNA-181a, which is known to be upregulated in HDF senescence, was also analyzed, and indeed, its expression was significantly increased in old cells at 21% O2 compared to those at 5% O2. Upregulation of MMP1 and downregulation of COL1A1 along with increased DNA damage were also observed under 21% O2 vs 5% O2. The data highlight that chronic exposure to atmospheric 21% O2 is able to trigger hormetic adaptive responses in HDF that however fail, in the long term, to prevent cellular aging. This information could be useful in further investigating molecular mechanisms involved in adaptation of skin fibroblasts to oxidative stress and may provide useful hints in addressing antiaging strategies

ATP independent proteasomal degradation of NQO1 in BL cell lines

Human NAD(P)H: quinone oxidoreductase 1 (NQO1) catalyzes the obligatory two-electron reduction of quinones. For this peculiar catalytic mechanism, the enzyme is considered an important cytoprotector. The NQO1 gene is expressed in all human tissues, unless a polymorphism due to C609T point mutation is present. This polymorphism produces a null phenotype in the homozygous condition and reduced enzyme activity in the heterozygous one. We previously demonstrated that two cell lines of haematopoietic origin, HL60 and Raji cells, possess the same heterozygous genotype, but different phenotypes; as expected for a heterozygous condition the HL60 cell line showed a low level of enzyme activity, while the Raji cell line appeared as null phenotype. The level of NQO1 mRNA was similar in the two cell lines and the different phenotype was not due to additional mutations or to expression of alternative splicing products. Here we show that in Raji BL cell line with heterozygous genotype the null NQO1 phenotype is due to 20S proteasome degradation of wild type and mutant protein isoforms and is not directly linked to C609T polymorphism. This finding may have important implications in B-cell differentiation, in leukaemia risk evaluation and in chemotherapy based on proteasome inhibitors